Reversible deactivation of motor cortex reveals that areas in parietal cortex are differentially dependent on motor cortex for the generation of movement.

Primates are characterized by specializations for manual manipulation, including expansion of posterior parietal cortex (PPC) and, in Catarrhines, evolution of a dexterous hand and opposable thumb. Previous studies examined functional interactions between motor cortex and PPC in New World monkeys and galagos, by inactivating M1 and evoking movements from PPC. These studies found that portions of PPC depend on M1 to generate movements. We now add a species that more closely resembles humans in hand morphology and PPC: macaques. Inactivating portions of M1 resulted in all evoked movements being reduced (28%) or completely abolished (72%) at the PPC sites tested (in areas 5L, PF, and PFG). Anterior parietal area 2 was similarly affected (26% reduced and 74% abolished) and area 1 was the least affected (12% no effect, 54% reduced, and 34% abolished). Unlike previous studies in New World monkeys and galagos, interactions between both nonanalogous (heterotopic) and analogous (homotopic) M1 and parietal movement domains were commonly found in most areas. These experiments demonstrate that there may be two parallel networks involved in motor control: a posterior parietal network dependent on M1 and a network that includes area 1 that is relatively independent of M1. Furthermore, it appears that the relative size and number of cortical fields in parietal cortex in different species correlates with homotopic and heterotopic effect prevalence. These functional differences in macaques could contribute to more numerous and varied muscle synergies across major muscle groups, supporting the expansion of the primate manual behavioral repertoire observed in Old World monkeys.NEW & NOTEWORTHY Motor cortex and anterior and posterior parietal cortex form a sensorimotor integration network. We tested the extent to which parietal areas could initiate movements independent of M1. Our findings support the contention that, although areas 2, 5L, PF, and PFG are highly dependent on M1 to produce movement, area 1 may constitute a parallel corticospinal pathway that can function somewhat independently of M1. A similar functional architecture may underlie dexterous tool use in humans.

Clinical implications of preoperative echocardiographic findings on cardiovascular outcomes following vascular surgery: An observational trial.

INTRODUCTION: Peripheral artery disease and cardiac disease are often comorbid conditions. Echocardiography is a diagnostic tool that can be performed preoperatively to risk stratify patients by a functional cardiac test. We hypothesized that ventricular dysfunction and valvular lesions were associated with an increased incidence of expanded major adverse cardiac events (Expanded MACE). METHODS AND MATERIALS: Retrospective cohort study from 2011 to 2020 including all patients from a major academic center who had vascular surgery and an echocardiographic study within two years of the index procedure. RESULTS: 813 patients were included in the study; a majority had a history of smoking (86%), an ASA score of 3 (65%), and were male (68%). Carotid endarterectomy was the most common surgery (24%) and the least common surgery was open abdominal aortic aneurysm repair (5%). We found no significant association between the echocardiographic findings of left ventricular dysfunction, right ventricular dysfunction, or valvular lesions and the postoperative development of Expanded MACE. CONCLUSIONS: The preoperative echocardiographic findings of left ventricular dysfunction, right ventricular dysfunction and moderate to severe valvular lesions were not predictive of an increased incidence of postoperative Expanded MACE. We identified a significant association between RV dysfunction and post-operative dialysis that should be interpreted carefully due to the small number of outcomes. The transition from open to endovascular surgery and advances in perioperative management may have led to improved cardiovascular outcomes. TRIAL REGISTRATION: Trial Registration: NCT04836702 (clinicaltrials.gov). https://www.google.com/search?client=firefox-b-d&q=NCT04836702.

Coevolution of motor cortex and behavioral specializations associated with flight and echolocation in bats.

Bats have evolved behavioral specializations that are unique among mammals, including self-propelled flight and echolocation. However, areas of motor cortex that are critical in the generation and fine control of these unique behaviors have never been fully characterized in any bat species, despite the fact that bats compose ∼25% of extant mammalian species. Using intracortical microstimulation, we examined the organization of motor cortex in Egyptian fruit bats (Rousettus aegyptiacus), a species that has evolved a novel form of tongue-based echolocation.1,2 We found that movement representations include an enlarged tongue region containing discrete subregions devoted to generating distinct tongue movement types, consistent with their behavioral specialization generating active sonar using tongue clicks. This magnification of the tongue in motor cortex is comparable to the enlargement of somatosensory representations in species with sensory specializations.3-5 We also found a novel degree of coactivation between the forelimbs and hindlimbs, both of which are involved in altering the shape and tension of wing membranes during flight. Together, these findings suggest that the organization of motor cortex has coevolved with peripheral morphology in bats to support the unique motor demands of flight and echolocation.

Distributed Motor Control of Limb Movements in Rat Motor and Somatosensory Cortex: The Sensorimotor Amalgam Revisited.

Which areas of the neocortex are involved in the control of movement, and how is motor cortex organized across species? Recent studies using long-train intracortical microstimulation demonstrate that in addition to M1, movements can be elicited from somatosensory regions in multiple species. In the rat, M1 hindlimb and forelimb movement representations have long been thought to overlap with somatosensory representations of the hindlimb and forelimb in S1, forming a partial sensorimotor amalgam. Here we use long-train intracortical microstimulation to characterize the movements elicited across frontal and parietal cortex. We found that movements of the hindlimb, forelimb, and face can be elicited from both M1 and histologically defined S1 and that representations of limb movement types are different in these two areas. Stimulation of S1 generates retraction of the contralateral forelimb, while stimulation of M1 evokes forelimb elevation movements that are often bilateral, including a rostral region of digit grasping. Hindlimb movement representations include distinct regions of hip flexion and hindlimb retraction evoked from S1 and hip extension evoked from M1. Our data indicate that both S1 and M1 are involved in the generation of movement types exhibited during natural behavior. We draw on these results to reconsider how sensorimotor cortex evolved.

The Multiple Representations of Complex Digit Movements in Primary Motor Cortex Form the Building Blocks for Complex Grip Types in Capuchin Monkeys.

In the present study, we investigated motor cortex (M1) and a small portion of premotor and parietal cortex using intracortical microstimulation in anesthetized capuchin monkeys. Capuchins are the only New World monkeys that have evolved an opposable thumb and use tools in the wild. Like most Old World monkeys and humans, capuchin monkeys have highly dexterous hands. We surveyed a large extent of M1 and found that ~22% of all evoked movements in M1 involved the digits, and the majority of these consisted of finger flexions and extensions. Different subtypes of movements could be identified, including opposable movements of digits 1 and 2 (D1 and D2). Interestingly, the pattern of such movements varied between animals. In one case, movements involved the adduction of the medial surface of D1 toward the lateral surface of D2, whereas in the other case, the tips of D1 and D2 came in contact. Unlike other primates examined, we also found extensive representations of the prehensile foot and tail. We propose that the manual behavioral repertoire of capuchin monkeys, which includes the use of tools in the wild, is well represented within the motor cortex in the form of muscle synergies between different body parts that compose these larger, complex behaviors.SIGNIFICANCE STATEMENT The ability to use tools is a milestone in human evolution. Capuchin monkeys are one of the few non-human primates that use tools in the wild. The present study is the first detailed exploration of the motor cortex of these primates using long-train intracortical microstimulation. Within primary motor cortex, we evoked finger movements involving flexions and extensions of multiple digits, or of the first and second digits alone. Interestingly, flexion of tail and toes could also be evoked. Together, these results suggest that the functional organization of the motor cortex represents not just muscles of the body, but muscle synergies that form the building blocks of the complex behavioral repertoire of these animals.

The Evolution of the Pulvinar Complex in Primates and Its Role in the Dorsal and Ventral Streams of Cortical Processing.

Current evidence supports the view that the visual pulvinar of primates consists of at least five nuclei, with two large nuclei, lateral pulvinar ventrolateral (PLvl) and central lateral nucleus of the inferior pulvinar (PIcl), contributing mainly to the ventral stream of cortical processing for perception, and three smaller nuclei, posterior nucleus of the inferior pulvinar (PIp), medial nucleus of the inferior pulvinar (PIm), and central medial nucleus of the inferior pulvinar (PIcm), projecting to dorsal stream visual areas for visually directed actions. In primates, both cortical streams are highly dependent on visual information distributed from primary visual cortex (V1). This area is so vital to vision that patients with V1 lesions are considered "cortically blind". When the V1 inputs to dorsal stream area middle temporal visual area (MT) are absent, other dorsal stream areas receive visual information relayed from the superior colliculus via PIp and PIcm, thereby preserving some dorsal stream functions, a phenomenon called "blind sight". Non-primate mammals do not have a dorsal stream area MT with V1 inputs, but superior colliculus inputs to temporal cortex can be more significant and more visual functions are preserved when V1 input is disrupted. The current review will discuss how the different visual streams, especially the dorsal stream, have changed during primate evolution and we propose which features are retained from the common ancestor of primates and their close relatives.

Cortical projections to the superior colliculus in grey squirrels (Sciurus carolinensis).

The superior colliculus is an important midbrain structure involved with integrating information from varying sensory modalities and sending motor signals to produce orienting movements towards environmental stimuli. Because of this role, the superior colliculus receives a multitude of sensory inputs from a wide variety of subcortical and cortical structures. Proportionately, the superior colliculus of grey squirrels is among the largest in size of all studied mammals, suggesting the importance of this structure in the behavioural characteristics of grey squirrels. Yet, our understanding of the connections of the superior colliculus in grey squirrels is lacking, especially with respect to possible cortical influences. In this study, we placed anatomical tracer injections within the medial aspect of the superior colliculus of five grey squirrels (Sciurus carolinensis) and analysed the areal distribution of corticotectal projecting cells in flattened cortex. V1 projections to the superior colliculus were studied in two additional animals. Our results indicate that the superior colliculus receives cortical projections from visual, higher order somatosensory, and higher order auditory regions, as well as limbic, retrosplenial and anterior cingulate cortex. Few, if any, corticotectal projections originate from primary motor, primary somatosensory or parietal cortical regions. This distribution of inputs is similar to the distribution of inputs described in other rodents such as rats and mice, yet the lack of inputs from primary somatosensory and motor cortex is features of corticotectal inputs more similar to those observed in tree shrews and primates, possibly reflecting a behavioural shift from somatosensory (vibrissae) to visual navigation.

Architectonic characteristics of the visual thalamus and superior colliculus in titi monkeys.

Titi monkeys are arboreal, diurnal New World monkeys whose ancestors were the first surviving branch of the New World radiation. In the current study, we use cytoarchitectonic and immunohistochemical characteristics to compare titi monkey subcortical structures associated with visual processing with those of other well-studied primates. Our goal was to appreciate features that are similar across all New World monkeys, and primates in general, versus those features that are unique to titi monkeys and other primate taxa. We examined tissue stained for Nissl substance, cytochrome oxidase (CO), acetylcholinesterase (AChE), calbindin (Cb), parvalbumin (Pv), and vesicular glutamate transporter 2 (VGLUT2) to characterize the superior colliculus, lateral geniculate nucleus, and visual pulvinar. This is the first study to characterize VGLUT2 in multiple subcortical structures of any New World monkey. Our results from tissue processed for VGLUT2, in combination with other histological stains, revealed distinct features of subcortical structures that are similar to other primates, but also some features that are slightly modified compared to other New World monkeys and other primates. These included subdivisions of the inferior pulvinar, sublamina within the stratum griseum superficiale (SGS) of the superior colliculus, and specific koniocellular layers within the lateral geniculate nucleus. Compared to other New World primates, many features of the subcortical structures that we examined in titi monkeys were most similar to those in owl monkeys and marmosets, with the lateral geniculate nucleus consisting of two main parvocellular layers and two magnocellular layers separated by interlaminar zones or koniocellular layers.

Representations of Fine Digit Movements in Posterior and Anterior Parietal Cortex Revealed Using Long-Train Intracortical Microstimulation in Macaque Monkeys.

The current investigation in macaque monkeys utilized long-train intracortical microstimulation to determine the extent of cortex from which movements could be evoked. Not only were movements evoked from motor areas (PMC and M1), but they were also evoked from posterior parietal (5, 7a, 7b) and anterior parietal areas (3b, 1, 2). Large representations of digit movements involving only the index finger (D2) and thumb (D1), were elicited from areas 1, 2, 7b, and M1. Other movements evoked from these regions were similar to ethologically relevant movements that have been described in other primates. These include combined forelimb and mouth movements and full hand grasps. However, many other movements were much more complex and could not be categorized into any of the previously described ethological categories. Movements involving specific digits, which mimic precision grips, are unique to macaques and have not been described in New World or prosimian primates. We propose that these multiple and expanded motor representations of the digits co-evolved with the emergence of the opposable thumb and alterations in grip type in some anthropoid lineages.

Vascular Graft Infection: Incidence and Potential Risk Factors.

PURPOSE: The purpose of this study was to identify factors that increase the risk of vascular graft infections (VGI) in patients following abdominal or lower extremity revascularization surgery. DESIGN: Retrospective, descriptive study. METHODS: We reviewed the electronic health records of 223 patients who had undergone abdominal or lower extremity revascularization procedures from July 2012 to November 2014, looking for factors associated with VGI. We reviewed 28 preoperative, intraoperative, and post-operative factors. Descriptive statistics (mean, range, and standard deviation) were used to describe the sample; χ was used to determine correlations between the risk factors and subsequent VGIs. The level of significance was determined at P = .05, with a confidence level of 95%. RESULTS: We identified 33 cases of VGIs for the 223 charts reviewed, yielding an incidence rate of 15%. Seventeen of the 33 patients with VGI (51.5%) were male. The average age of patients who experienced VGI was 60.9 years (standard deviation, 12.2 years, range, 29-81 years). Preoperative factors that were shown to show statistical significance for the development of VGI were sequential procedures (P = .003), diabetes mellitus (P = .002), hemoglobin A1c more than 7.0 (P = .0002), blood glucose more than 180 mg/dL (P = .0006), and lack of mobility (0.0097). Intraoperative factors associated with VGI were hemostatic agents applied to the surgical field intraoperatively (P = .003) and perioperative hypoxemia (P = .027). Postoperative factors associated with VGI were discharge from the hospital to skilled nursing facility or acute rehabilitation facility (P = .005) and unscheduled clinic visits (P = .008). CONCLUSION: We measured a 15% incidence of VGI and identified multiple pre-, intra-, and postoperative associated factors. Vigilance is required to prevent VGI and knowledge of specific risk factors is important.

The evolution and functions of nuclei of the visual pulvinar in primates.

In this review, we outline the history of our current understanding of the organization of the pulvinar complex of mammals. We include more recent evidence from our own studies of both New and Old World monkeys, prosimian galagos, and close relatives of primates, including tree shrews and rodents. Based on cumulative evidence, we provide insights into the possible evolution of the visual pulvinar complex, as well as the possible co-evolution of the inferior pulvinar nuclei and temporal cortical visual areas within the MT complex.

Intracortical Microstimulation Maps of Motor, Somatosensory, and Posterior Parietal Cortex in Tree Shrews (Tupaia belangeri) Reveal Complex Movement Representations.

Long-train intracortical microstimulation (LT-ICMS) is a popular method for studying the organization of motor and posterior parietal cortex (PPC) in mammals. In primates, LT-ICMS evokes both multijoint and multiple-body-part movements in primary motor, premotor, and PPC. In rodents, LT-ICMS evokes complex movements of a single limb in motor cortex. Unfortunately, very little is known about motor/PPC organization in other mammals. Tree shrews are closely related to both primates and rodents and could provide insights into the evolution of complex movement domains in primates. The present study investigated the extent of cortex in which movements could be evoked with ICMS and the characteristics of movements elicited using both short train (ST) and LT-ICMS in tree shrews. We demonstrate that LT-ICMS and ST-ICMS maps are similar, with the movements elicited with ST-ICMS being truncated versions of those elicited with LT-ICMS. In addition, LT-ICMS-evoked complex movements within motor cortex similar to those in rodents. More complex movements involving multiple body parts such as the hand and mouth were also elicited in motor cortex and PPC, as in primates. Our results suggest that complex movement networks present in PPC and motor cortex were present in mammals prior to the emergence of primates.

Resolving the organization of the territory of the third visual area: a new proposal.

In primates, the cortex adjoining the rostral border of V2 has been variously interpreted as belonging to a single visual area, V3, with dorsal V3 (V3d) representing the lower visual quadrant and ventral V3 (V3v) representing the upper visual quadrant, V3d and V3v constituting separate, incomplete visual areas, V3d and ventral posterior (VP), or V3d being divided into several visual areas, including a dorsomedial (DM) visual area, a medial visual area (M), and dorsal extension of VP (or VLP). In our view, the evidence from V1 connections strongly supports the contention that V3v and V3d are parts of a single visual area, V3, and that DM is a separate visual area along the rostral border of V3d. In addition, the retinotopy revealed by V1 connection patterns, microelectrode mapping, optical imaging mapping, and functional magnetic resonance imaging (fmri) mapping indicates that much of the proposed territory of V3d corresponds to V3. Yet, other evidence from microelectrode mapping and anatomical connection patterns supports the possibility of an upper quadrant representation along the rostral border of the middle of dorsal V2 (V2d), interpreted as part of DM or DM plus DI, and along the midline end of V2d, interpreted as the visual area M. While the data supporting these different interpretations appear contradictory, they also seem, to some extent, valid. We suggest that V3d may have a gap in its middle, possibly representing part of the upper visual quadrant that is not part of DM. In addition, another visual area, M, is likely located at the DM tip of V3d. There is no evidence for a similar disruption of V3v. For the present, we favor continuing the traditional concept of V3 with the possible modification of a gap in V3d in at least some primates.

Reversible deactivation of higher-order posterior parietal areas. II. Alterations in response properties of neurons in areas 1 and 2.

The role that posterior parietal (PPC) and motor cortices play in modulating neural responses in somatosensory areas 1 and 2 was examined with reversible deactivation by transient cooling. Multiunit recordings from neurons in areas 1 and 2 were collected from six anesthetized adult monkeys (Macaca mulatta) before, during, and after reversible deactivation of areas 5L or 7b or motor cortex (M1/PM), while select locations on the hand and forelimb were stimulated. Response changes were quantified as increases and decreases to stimulus-driven activity relative to baseline and analyzed during three recording epochs: during deactivation ("cool") and at two time points after deactivation ("rewarm 1," "rewarm 2"). Although the type of response change observed was variable, for neurons at the recording sites tested >90% exhibited a significant change in response during cooling of 7b while cooling area 5L or M1/PM produced a change in 75% and 64% of sites, respectively. These results suggest that regions in the PPC, and to a lesser extent motor cortex, shape the response characteristics of neurons in areas 1 and 2 and that this kind of feedback modulation is necessary for normal somatosensory processing. Furthermore, this modulation appears to happen on a minute-by-minute basis and may serve as the substrate for phenomena such as somatosensory attention.

Reversible deactivation of higher-order posterior parietal areas. I. Alterations of receptive field characteristics in early stages of neocortical processing.

Somatosensory processing in the anesthetized macaque monkey was examined by reversibly deactivating posterior parietal areas 5L and 7b and motor/premotor cortex (M1/PM) with microfluidic thermal regulators developed by our laboratories. We examined changes in receptive field size and configuration for neurons in areas 1 and 2 that occurred during and after cooling deactivation. Together the deactivated fields and areas 1 and 2 form part of a network for reaching and grasping in human and nonhuman primates. Cooling area 7b had a dramatic effect on receptive field size for neurons in areas 1 and 2, while cooling area 5 had moderate effects and cooling M1/PM had little effect. Specifically, cooling discrete locations in 7b resulted in expansions of the receptive fields for neurons in areas 1 and 2 that were greater in magnitude and occurred in a higher proportion of sites than similar changes evoked by cooling the other fields. At some sites, the neural receptive field returned to the precooling configuration within 5-22 min of rewarming, but at other sites changes in receptive fields persisted. These results indicate that there are profound top-down influences on sensory processing of early cortical areas in the somatosensory cortex.

Respiratory manganese particle size, time-course and neurobehavioral outcomes in workers at a manganese alloy production plant.

The progression of manganism with chronic exposure to airborne manganese (Mn) is not well understood. Here, we further investigate the findings on exposure and neurobehavioral outcomes of workers from a silico- and ferromanganese production plant and non-exposed workers from the same community in 1990 and 2004, using a variety of exposure metrics that distinguish particle size and origin within the range of respirable airborne exposures. Mn exposure matrices for large respirable particulate (Mn-LRP, dust) and small respirable particulate (Mn-SRP, fume), based on process origins, were used together with detailed work histories since 1973 (plant opening), to construct exposure metrics including burdens and cumulative burdens with various clearance half-lives. For three out of eight 1990 neurobehavioral tests analyzed with linear regression models, duration of Mn exposure was the best predictor: Luria-Nebraska Neuropsychological Battery - Motor Scale, Trail-Making B and Finger Tapping. The Luria-Nebraska Motor Scale had the strongest association (t ∼ 5.0, p < 10(-6)). For outcomes on three other tests, the duration and Mn-SRP metrics were comparable: Trail Making Test A, Cancellation H and Stroop Color-Word Test (color/word subtest). Delayed Word Recall was best predicted by Mn-SRP (based on square root or truncated air-concentrations). The Word score on the Stroop Color-Word Test was the only outcome for which Mn-LRP was the leading predictor (t = -2.92, p = 0.003), while performance on the WAIS-R Digit Span Test was not significantly predicted by any metric. For outcomes evaluated in both 1990 and 2004, a mixed-effect linear regression model was used to examine estimates of within-individual trends. Duration and Mn-SRP were associated with performance on the Luria-Nebraska Motor Scale, as well as with other outcomes that appeared to have both reversible and progressive features, including Trail Making A and B, Cancellation H and Delayed Word Recall. With the mixed-effect model, Digit Span exhibited a significant irreversible association with exposure duration (t = -2.34, p = 0.021) and Mn-SRP (square root; t = -2.38, p = 0.019) metrics. The strong prediction using duration of exposure is consistent with effective homeostatic regulation of tissue-level Mn in the observed exposure range of respirable Mn (< 0.2mg/m(3)).

Airborne manganese as dust vs. fume determining blood levels in workers at a manganese alloy production plant.

The appropriate exposure metrics for characterizing manganese (Mn) exposure associated with neurobehavioral effects have not been established. Blood levels of Mn (B-Mn) provide a potentially important intermediate marker of Mn airborne exposures. Using data from a study of a population of silicon- and ferro-manganese alloy production workers employed between 1973 and 1991, B-Mn levels were modeled in relation to prior Mn exposure using detailed work histories and estimated respirable Mn concentrations from air-sampling records. Despite wide variation in exposure levels estimated for individual jobs, duration of employment (exposure) was itself a strong predictor of B-Mn levels and strongest when an 80-day half-life was applied to contributions over time (t=6.95, 7.44, respectively; p<10(-5)). Partitioning exposure concentrations based on process origin into two categories: (1) "large" respirable particulate (Mn-LRP) derived mainly from mechanically generated dust, and (2) "small" respirable particulate (Mn-SRP) primarily electric furnace condensation fume, revealed that B-Mn levels largely track the small, fume exposures. With a half-life of 65 days applied in a model with cumulative exposure terms for both Mn-LRP (t=-0.16, p=0.87) and Mn-SRP (t=6.45, p<10(-5)), the contribution of the large-size fraction contribution was negligible. Constructing metrics based on the square root of SRP exposure concentrations produced a better model fit (t=7.87 vs. 7.44, R(2)=0.2333 vs. 0.2157). In a model containing both duration (t=0.79, p=0.43) and (square root) fume (t=2.47, p=0.01) metrics, the duration term was a weak contributor. Furnace-derived, small respirable Mn particulate appears to be the primary contributor to B-Mn levels, with a dose-rate dependence in a population chronically exposed to Mn, with air-concentrations declining in recent years. These observations may reflect the presence of homeostatic control of Mn levels in the blood and other body tissues and be useful in assessing Mn exposures for evaluating neurotoxic effects.