THE SMALL IRREGULAR ACTIVITY STATE IN THE RAT HIPPOCAMPUS

The sleeping rat cycles between two well characterized physiological states, slow-wave sleep (SWS) and rapid eye-movement sleep (REM), often identified by the presence of large irregular activity (LIA) and theta activity, respectively, in the hippocampal EEG. Inspection of the activity of ensembles of hippocampal CA1 complex-spike cells along with the EEG reveals the presence of a third physiological state, distinctly different from both REM and SWS in both hippocampal EEG and population activity. The EEG during this state abruptly flattens for a few seconds, appearing very similar to the "small-amplitude irregular activity" (SIA) hippocampal EEG state reported in the literature to occur when rats are startled out of sleep. The flattening of the EEG is accompanied by a striking pattern of spike activity in the population of hippocampal pyramidal cells, wherein a small subset of cells becomes very active while the rest become quiet; the same subset of cells is usually active across long sequences of SIA. This dissertation shows (1) that these active cells are place cells whose place fields are in the location in which the rat is sleeping; (2) that the spontaneous SIA observed during sleep corresponds to the SIA state of increased alertness that has been reported in the literature to occur when rats are startled out of sleep; (3) that SIA is accompanied by a desynchronized neocortical EEG and low amplitude EMG; (4) that the cells active in SIA reflect a memory for the location in which the rat fell asleep, rather than an assessment of its location based on current sensory information; and (5) that the generation of SIA is likely to involve an increase of serotonin levels in the medial septal nucleus. It is proposed that SIA serves as a neural substrate for maintaining context memory during sleep, and that it reflects a partial arousal in response to internal or external stimuli that allows the animal to assess whether full awakening is warranted, without disrupting the sleep cycle

Reach and grasp by people with tetraplegia using a neurally controlled robotic arm

Paralysis following spinal cord injury (SCI), brainstem stroke, amyotrophic lateral sclerosis (ALS) and other disorders can disconnect the brain from the body, eliminating the ability to carry out volitional movements. A neural interface system (NIS)1–5 could restore mobility and independence for people with paralysis by translating neuronal activity directly into control signals for assistive devices. We have previously shown that people with longstanding tetraplegia can use an NIS to move and click a computer cursor and to control physical devices6–8. Able-bodied monkeys have used an NIS to control a robotic arm9, but it is unknown whether people with profound upper extremity paralysis or limb loss could use cortical neuronal ensemble signals to direct useful arm actions. Here, we demonstrate the ability of two people with long-standing tetraplegia to use NIS-based control of a robotic arm to perform three-dimensional reach and grasp movements. Participants controlled the arm over a broad space without explicit training, using signals decoded from a small, local population of motor cortex (MI) neurons recorded from a 96-channel microelectrode array. One of the study participants, implanted with the sensor five years earlier, also used a robotic arm to drink coffee from a bottle. While robotic reach and grasp actions were not as fast or accurate as those of an able-bodied person, our results demonstrate the feasibility for people with tetraplegia, years after CNS injury, to recreate useful multidimensional control of complex devices directly from a small sample of neural signals

Physiological changes in the rat cerebellar cortex after motor-skill learning

Thesis (B.S.)--University of Illinois at Urbana-Champaign, 1998.Includes bibliographical reference (leaves 12-13)U of I OnlyTheses restricted to UIUC community onl

Article Functional Biases in Visual Cortex Neurons with Identified Projections to Higher Cortical Targets

Summary Background: Visual perception involves information flow from lower-to higher-order cortical areas, which are known to process different kinds of information. How does this functional specialization arise? As a step toward addressing this question, we combined fluorescent retrograde tracing with in vivo two-photon calcium imaging to simultaneously compare the tuning properties of neighboring neurons in areas 17 and 18 of ferret visual cortex that have different higher cortical projection targets. Results: Neurons projecting to the posterior suprasylvian sulcus (PSS) were more direction selective and preferred shorter stimuli, higher spatial frequencies, and higher temporal frequencies than neurons projecting to area 21, anticipating key differences between the functional properties of the target areas themselves. These differences could not be explained by a correspondence between anatomical and functional clustering within early visual cortex, and the largest differences were in properties generated within early visual cortex (direction selectivity and length preference) rather than in properties present in its retinogeniculate inputs. Conclusions: These projection cell groups, and hence the higher-order visual areas to which they project, likely obtain their functional properties not from biased retinogeniculate inputs but from highly specific circuitry within the cortex

Functional Biases in Visual Cortex Neurons with Identified Projections to Higher Cortical Targets

Background: Visual perception involves information flow from lower- to higher-order cortical areas, which are known to process different kinds of information. How does this functional specialization arise? As a step toward addressing this question, we combined fluorescent retrograde tracing with in vivo two-photon calcium imaging to simultaneously compare the tuning properties of neighboring neurons in areas 17 and 18 of ferret visual cortex that have different higher cortical projection targets. Results: Neurons projecting to the posterior suprasylvian sulcus (PSS) were more direction selective and preferred shorter stimuli, higher spatial frequencies, and higher temporal frequencies than neurons projecting to area 21, anticipating key differences between the functional properties of the target areas themselves. These differences could not be explained by a correspondence between anatomical and functional clustering within early visual cortex, and the largest differences were in properties generated within early visual cortex (direction selectivity and length preference) rather than in properties present in its retinogeniculate inputs. Conclusions: These projection cell groups, and hence the higher-order visual areas to which they project, likely obtain their functional properties not from biased retinogeniculate inputs but from highly specific circuitry within the cortex.Ruth L. Kirschstein National Research Service Award (5F32NS054390)National Institutes of Health (U.S.) (Grant EY018648)National Institutes of Health (U.S.) (Grant EY07023)National Institutes of Health (U.S.) (Grant DP1 OD003646)National Institutes of Health (U.S.) (Grant EB006385

Mood and quality of life in patients treated with brain-responsive neurostimulation: The value of earlier intervention

•Responsive neurostimulation is a safe and effective treatment for focal-onset seizures.•Patients treated within 10 years of epilepsy onset improved in mood and QoL.•Those treated after 20 years did not, despite similar seizure frequency reductions.•These results underscore the importance of early, effective treatment. To establish whether earlier treatment using direct brain-responsive neurostimulation for medically intractable focal-onset seizures is associated with better mood and Quality of Life (QoL) compared to later treatment intervention. Data were retrospectively analyzed from prospective clinical trials of a direct brain-responsive neurostimulator (RNS® System) for treatment of adults with medically intractable focal-onset epilepsy. Participants completed the Quality of Life in Epilepsy Inventory (QOLIE-31) yearly through 9 years of follow-up and the Beck Depression Inventory-II (BDI-II) through 2 years of follow-up. Changes in each assessment after treatment with responsive neurostimulation were calculated for patients who began treatment within 10 years of seizure onset (early) and those who began treatment 20 years or more after seizure onset (late). The median duration of epilepsy was 18.3 years at enrollment. At 9 years, both the early (N = 51) and late (N = 109) treatment groups experienced similar and significant reductions in the frequency of disabling seizures (73.4% and 77.8%, respectively). The early treatment patients had significant improvements in QoL and mood. However, the late treatment patients not only failed to show these improvements but also declined in the emotional QoL subscale. Patients treated with brain-responsive neurostimulation earlier in the course of their epilepsy show significant improvements in multiple domains of QoL and mood that are not observed in patients treated later in the course of their epilepsy despite similar efficacy in seizure reduction. Even with similar and substantial reductions in seizure frequency, the comorbidities of uncontrolled epilepsy may be less responsive to treatment when too many years have passed. The results of this study suggest that, as with resective and ablative surgery, treatment with brain-responsive neurostimulation should be delivered as early as possible in the course of medically resistant epilepsy to maximize the opportunity for improvements in mood and QoL