Adapting a Neural Engineering Summer Camp for High School Students to a Fully Online Experience.

The COVID-19 pandemic and its resulting health and safety concerns caused the cancellation of many engineering education opportunities for high school students. To expose high school students to the field of neural engineering and encourage them to pursue academic pathways in biomedical engineering, the Center for Neurotechnology (CNT) at the University of Washington converted an in-person summer camp to a fully online program (Virtual REACH Program, VRP) offering both synchronous and asynchronous resources. The VRP is a five-day online program that focuses on a different daily theme (neuroscience, brain-computer interfaces, electrical stimulation, neuroethics, career/academic pathways). Each day, the VRP starts with a live videoconference meeting (lecture and interactive discussion) with a CNT faculty member. The online lectures are supported by at-home learning resources (e.g., text, videos, activities, quizzes) embedded within a digital book created using the Pressbook platform. An online bulletin board (Padlet) is also used by students to share artifacts and build community. Program evaluation will be conducted by an external evaluator. A summative survey will collect information on participants' experiences in the VRP and will help inform future iterations of the program. Although significant time was required to create a digital book, the VRP will reach a larger audience than the prior in-person program and resulted in the creation of learning tools that can be used in the future.

Insights into the histology of planarian flatworm Phagocata gracilis based on location specific, intact lipid information provided by GCIB-ToF-SIMS imaging.

Planarian flatworms are known as the masters of regeneration, re-growing an entire organism from as little as 1/279th part of their body. While the proteomics of these processes has been studied extensively, the planarian lipodome remains relatively unknown. In this study we investigate the lipid profile of planarian tissue sections with imaging Time-of-Flight - Secondary-Ion-Mass-Spectrometry (ToF-SIMS). ToF-SIMS is a label-free technique capable of gathering intact, location specific lipid information on a cellular scale. Lipid identities are confirmed using LC-MS/MS. Our data shows that different organ structures within planarians have unique lipid profiles. The 22-carbon atom poly unsaturated fatty acids (PUFAs) which occur in unusually high amounts in planarians are found to be mainly located in the testes. Additionally, we observe that planarians contain various odd numbered fatty acid species, that are usually found in bacteria, localized in the reproductive and ectodermal structures of the planarian. An abundance of poorly understood ether fatty acids and ether lipids were found in unique areas in planarians as well as a new, yet unidentified class of potential lipids in planarian intestines. Identifying the location of these lipids in the planarian body provides insights into their bodily functions and, in combination with knowledge about their diet and their genome, enables drawing conclusions about planarian fatty acid processing.

New Perspectives on Neuroengineering and Neurotechnologies: NSF-DFG Workshop Report.

GOAL: To identify and overcome barriers to creating new neurotechnologies capable of restoring both motor and sensory function in individuals with neurological conditions. METHODS: This report builds upon the outcomes of a joint workshop between the US National Science Foundation and the German Research Foundation on New Perspectives in Neuroengineering and Neurotechnology convened in Arlington, VA, USA, November 13-14, 2014. RESULTS: The participants identified key technological challenges for recording and manipulating neural activity, decoding, and interpreting brain data in the presence of plasticity, and early considerations of ethical and social issues pertinent to the adoption of neurotechnologies. CONCLUSIONS: The envisaged progress in neuroengineering requires tightly integrated hardware and signal processing efforts, advances in understanding of physiological adaptations to closed-loop interactions with neural devices, and an open dialog with stakeholders and potential end-users of neurotechnology. SIGNIFICANCE: The development of new neurotechnologies (e.g., bidirectional brain-computer interfaces) could significantly improve the quality of life of people living with the effects of brain or spinal cord injury, or other neurodegenerative diseases. Focused efforts aimed at overcoming the remaining barriers at the electrode tissue interface, developing implantable hardware with on-board computation, and refining stimulation methods to precisely activate neural tissue will advance both our understanding of brain function and our ability to treat currently intractable disorders of the nervous system.

A key role of the basal ganglia in pain and analgesia--insights gained through human functional imaging.

The basal ganglia (BG) are composed of several nuclei involved in neural processing related to the execution of motor, cognitive and emotional activities. Preclinical and clinical data have implicated a role for these structures in pain processing. Recently neuroimaging has added important information on BG activation in conditions of acute pain, chronic pain and as a result of drug effects. Our current understanding of alterations in cortical and sub-cortical regions in pain suggests that the BG are uniquely involved in thalamo-cortico-BG loops to integrate many aspects of pain. These include the integration of motor, emotional, autonomic and cognitive responses to pain.

Nociceptive behavioral responses to chemical, thermal and mechanical stimulation after unilateral, intrastriatal administration of 6-hydroxydopamine.

The basal ganglia are involved not only with motor processes such as posture, pre-movement planning and movement initiation, but also with the processing and modulation of nociceptive somatosensory information. In the current studies, unilateral, intrastriatal 6-hydroxydopamine (6-OHDA) was used to investigate how dopamine depletion alters nociceptive behavioral responses to chemical, thermal and mechanical stimulation in rats. Compared to control rats injected with intrastriatal saline, rats depleted of dopamine displayed increased nociceptive responses to chemical stimulation of the face and hyperalgesic responses to thermal stimulation of the hind paw without alterations in rearing behavior or body weight gain. Minor changes were observed in the response to mechanical stimulation of the hind paws and face. These data provide further evidence that the dopaminergic nigrostriatal pathway plays a role in the modulation of nociceptive information.

Behavioural responses following tooth injury in rats.

Early changes in spontaneous behaviour (exploration, grooming, freezing, rearing, jaw motion, yawning) and body weight were measured at two and three days after pulp exposure injury and implantation of Fluorogold (FG) into molar teeth of rats. Rats with FG and injuries to three teeth gained weight less rapidly, explored less frequently and froze more often than sham-operated rats. Yawning was not observed in any rats prior to surgery and it was seen more frequently in tooth-injured rats than in sham-operated rats. These results suggest that careful observation of spontaneous behaviour after tooth injuries can be used to assess dental pain in rats and may provide behavioural markers to correlate with anatomical changes after injury. The dental nerve cell bodies that had accumulated transported FG were medium to large, and they only co-localized calcitonin gene-related peptide (CGRP) in a subset of the medium neurons. Chromatolytic or moribund FG-labelled neurons were also found.

Behavioral and electrophysiological consequences of deafferentation following chronic constriction of the infraorbital nerve in adult rats.

Deafferentation of the hind paw following sciatic nerve injury results in behavioral changes, such as autotomy, suggestive of persistent, spontaneous pain. The effects of deafferentation involving trigeminal nerves have, however, received less attention. Here, alterations in trigeminal ganglion neuronal activity and mechanically evoked and spontaneous behavior were studied in adult rats after a chronic constriction injury of the infraorbital nerve (ION). Compared to sham-operated rats, most rats with ION damage were unresponsive to mechanical stimulation of the mystacial vibrissae up to 56 days after surgery. Increased facial grooming was observed only in rats with chronic ION constriction 10 days after surgery. Free-ranging behavior was similar to that of sham-injury animals. In contrast, increases in the number of spontaneously active trigeminal ganglion neurones were observed in those rats with ION injuries at both 3 and 56 days. These data suggest that chronic constrictive injuries of the ION resulting in prolonged loss of low-threshold input from the periphery lead to only transient behavioral changes, despite the presence of spontaneous activity in trigeminal sensory neurones.

Trigeminal ganglion neuronal activity and glial fibrillary acidic protein immunoreactivity after inferior alveolar nerve crush in the adult rat.

Nerve injury to the mandibular division of the trigeminal nerve has been shown to cause satellite cell reactions that extend beyond the mandibular division of the trigeminal ganglion into the maxillary and ophthalmic divisions. The goal of this study was to determine whether any physiological abnormalities correlated with this dispersal of satellite cell reaction. We investigated the electrophysiological and satellite cell glial fibrillary acidic protein immunoreactivity (GFAP-IR) changes that occur within the trigeminal ganglion 3, 10 and 59 days after a crush injury of the inferior alveolar nerve (IAN). At 3 days after IAN crush, there were no mechanically-evoked responses to ipsilateral stimulation of the skin and intraoral structures (e.g., mandibular incisor, lower lip and rostral mandibular gingiva) innervated by the IAN. However, the peripheral representations of the auriculotemporal, mylohyoid, lingual and maxillary nerve were intact and no abnormal responses to mechanical stimulation were detected to stimulation of tissue innervated by these nerves. By 10 days after the IAN crush, mandibular neurons responded to mechanical and electrical stimuli of the peripheral receptive field of the IAN, but with slower conduction velocities and higher electrical thresholds compared to control values. These abnormal electrophysiological response characteristics persisted 59 days following nerve injury. At 3, 10 and 59 days after IAN crush, 3-4% of the recorded mandibular neurons displayed spontaneous activity that was never observed in rats without nerve injury. Spontaneous activity was also never observed in neurons recorded in the maxillary or ophthalmic divisions of the trigeminal ganglion. Intense GFAP-IR in satellite cells was observed surrounding a mean of 131.7 neurons/section within the mandibular division of the trigeminal ganglion 3 days after nerve injury and around 50.3 neurons/section at 10 days. GFAP-IR was also present surrounding 16.5 and 10.3 neurons/section in the maxillary division of the trigeminal nerve at 3 and 10 days, respectively. At 59 days after IAN crush, GFAP-IR satellite cells were found around 22.9 neurons/section in the mandibular division of the trigeminal nerve, but were not found elsewhere in the trigeminal ganglion. The more extensive distribution of neurons encircled by satellite cell GFAP-IR compared to the trigeminal ganglion region containing abnormal electrophysiological responses demonstrates that abnormal neuronal signaling may not be characteristic of trigeminal ganglion neurons that are surrounded by GFAP injury reactions. However, the persistence of GFAP-IR 59 days after nerve injury suggests that satellite cell GFAP is involved in the long-term recovery of injured neurons.

The role of the basal ganglia in nociception and pain.

The involvement of the basal ganglia in motor functions has been well studied. Recent neurophysiological, clinical and behavioral experiments indicate that the basal ganglia also process non-noxious and noxious somatosensory information. However, the functional significance of somatosensory information processing within the basal ganglia is not well understood. This review explores the role of the striatum, globus pallidus and substantia nigra in nociceptive sensorimotor integration and suggests several roles of these basal ganglia structures in nociception and pain. Electrophysiological experiments have detailed the non-nociceptive and nociceptive response properties of basal ganglia neurons. Most studies agree that some neurons within the basal ganglia encode stimulus intensity. However, these neurons do not appear to encode stimulus location since the receptive fields of these cells are large. Many basal ganglia neurons responsive to somatosensory stimulation are activated exclusively or differentially by noxious stimulation. Indirect techniques used to measure neuronal activity (i.e., positron emission tomography and 2-deoxyglucose methods) also indicate that the basal ganglia are activated differentially by noxious stimulation. Neuroanatomical experiments suggest several pathways by which nociceptive information may reach the basal ganglia. Neuroanatomical studies have also indicated that the basal ganglia are rich in many different neuroactive chemicals that may be involved in the modulation of nociceptive information. Microinjection of opiates, dopamine and gamma-aminobutyric acid (GABA) into the basal ganglia have varied effects on pain behavior. Administration of these neurochemicals into the basal ganglia affects supraspinal pain behaviors more consistently than spinal reflexive behaviors. The reduction of pain behavior following electrical stimulation of the substantia nigra and caudate nucleus provides additional evidence for a role of the basal ganglia in pain modulation. Some patients with basal ganglia disease (e.g., Parkinson's disease, Huntington's disease) have alterations in pain sensation in addition to motor abnormalities. Frequently, these patients have intermittent pain that is difficult to localize. Collectively, these data suggest that the basal ganglia may be involved in the (1) sensory-discriminative dimension of pain, (2) affective dimension of pain, (3) cognitive dimension of pain, (4) modulation of nociceptive information and (5) sensory gating of nociceptive information to higher motor areas. Further experiments that correlate neuronal discharge activity with stimulus intensity and escape behavior in operantly conditioned animals are necessary to fully understand how the basal ganglia are involved in nociceptive sensorimotor integration.

Tooth pulp-evoked potentials in the monkey: cortical surface and intracortical distribution.

The distribution of tooth pulp-evoked potentials (TPEPs) was characterized in the primary motor (MI), primary somatosensory (SI) and secondary somatosensory (SII) cortices of the monkey. Bipolar electrical tooth pulp stimulation elicited TPEP components P23 and N44 over SI, P26 and N72 over MI, and P72, N161, P280, N420, P561 and N662 over SII. Muscular artifacts and extradental input did not affect the TPEP as demonstrated by experiments using a neuromuscular blocking agent and removal of the pulp, respectively. The short latency TPEPs recorded over SI and MI were evoked by low stimulus intensities and activation of A beta nerve fibers, whereas the long latency TPEPs recorded over SII required higher stimulus intensities and the additional recruitment of A delta nerve fibers. Intracortical recordings revealed polarity reversals of components P23 and N44 in area 3b, P26 and N72 in area 4, and P72, N161, P280, N420, P561 and N662 in the upper bank of the lateral sulcus (SII). Evidence presented in this study suggests that TPEPs recorded from SI and MI relate to non-nociceptive mechanisms while TPEPs recorded from SII relate to nociceptive mechanisms.

Neuroma pain model: correlation of motor behavior and body weight with autotomy in rats.

A rat pain model was investigated by examining the correlation of autotomy (self-mutilation) score with motor behavior and body weight change after sciatic nerve transection, encapsulation and neuroma formation. Observations of motor behavior and body weight changes (e.g. feeding behavior) as an index of pain were considered to have several advantages over scoring the degree of autotomy. Motor activity of 14 rats (12 neuroma, 2 sham), measured using a stabilimeter, was compared on a weekly basis to autotomy scores for a total of 7 weeks after surgery. Additionally, body weight of 26 rats (20 neuroma, 6 sham surgery) was monitored for 4 weeks following surgery. While autotomy, changes in body weight and abnormalities in motor behavior were observed after surgery, no significant Spearman rank correlation coefficients were determined for any week and thus no significant relationships were found between autotomy score and motor activity or body weight. However, it was observed that rats after sham surgery gained significantly more weight than rats after sciatic nerve transection. Therefore, these results cast doubt on the validity of autotomy score as the sole index of pain.