Ventral Lesions Research Articles

Synapse preservation and decreased glial reactions following ventral root crush (VRC) and treatment with 4-hydroxy-tempo (TEMPOL).

Astrogliosis and microglial reactions are correlated with the formation of scar tissue and synapse loss. 4-hydroxy-tempo (TEMPOL) is a reactive oxygen species scavenger with proven neuroprotective efficacy in experimental models of traumatic injury and cerebral ischemia. TEMPOL has not, however, been applied following ventral root lesions, which are particularly correlated with the degeneration of spinal motoneurons following brachial plexus injuries. Thus, the present study investigated the effects of TEMPOL on motoneurons and adjacent glial reactions, with a particular focus on the preservation of excitatory and inhibitory spinal circuits. Adult female Sprague Dawley rats were subjected to ventral root crush (VRC) at the lumbar intumescence. Animals were divided into the following experimental groups: (a) VRC-saline treatment; (b) VRC-TEMPOL treatment (12mg/kg, n=5), and (c) VRC-TEMPOL treatment (250mg/kg, n=5). The spinal cord tissue located contralateral to the lesion was used as the control. Fourteen days after lesioning, the rats were euthanized and the spinal cords were removed for motoneuron counting and immunolabeling with glial (GFAP and Iba-1) and synapse markers (synaptophysin, VGLUT-1, and GAD65). Although TEMPOL did not exert neuroprotective effects at the studied concentrations, the modulation of glial reactions was significant at higher doses. Thus, synaptophysin staining was preserved and, in particular, VGLUT-1-positive inputs were maintained, thereby indicating that TEMPOL preserved proprioceptive glutamatergic inputs without exacerbating the rate of motoneuron degeneration. Consequently, its administration with other efficient neuroprotective substances may significantly improve the outcomes following spinal cord lesioning.

Large Osteochondroma of the Scapula in a 2-Year-Old

Abstract Osteochondromas are a common tumour comprising up to 40% of benign bone tumours. Malignant transformation of osteochondromas is quite rare but increases based on genetics (EXT gene mutation) as well as location (pelvis and scapula). Osteochondromas of the scapula generally present once they reach a size that disrupts scapulothoracic motion or is noticed as an obvious palpable mass around the scapula. Here we present a case report of a 2-year-old boy with a large circumferential osteochondroma of the right scapula. Due to the size, location and rapid expansion of the mass, concerns for malignancy were quite high. On MRI examination, T2 imaging revealed an unimpressive cartilage cap but with substantial destruction of bone and mass effect causing alteration of the architecture of the surrounding ribs. On surgical excision of the lesion, the neurovascular bundle was found to be anterior to the mass and a small, thin, misshapen scapula was left following excision. Concerning features for malignant transformation include rapid expansion, growth after skeletal maturity as well as a cartilage cap >2 cm in size. Pathologic specimen was sent, ensuring the inclusion of a portion of the underlying scapula for assessment. Results of pathology revealed a benign lesion without signs of atypia in the lesion or scapular specimen sent. Osteochondromas of the scapula should be followed closely for many reasons. First there is an increased risk of malignancy in these lesions, particularly in a large, rapidly expanding lesion. Secondly, due to the location of the lesion, consequences of mass effect are more substantial due to disruption of scapulothoracic rhythm and the potential for joint injury distal to the scapula. Third, because of its hidden nature, ventral lesions may go unnoticed, and any abnormality of scapular positioning or movement should prompt further investigation of the architecture of the scapula.

Exploring the Dendritic Spine Pathology in a Schizophrenia-related Neurodevelopmental Animal Model

Schizophrenia is a neurodevelopmental disorder identified by psychotic episodes, as well as cognitive deficits. There are reports of multiple alterations in the brain in schizophrenia, such as fewer dendritic spines with shape abnormalities in cortical and subcortical areas. A correlation has been established between shape and function in dendritic spines; and as the main site of excitatory synapses, the dendritic spine pathology represents a potential target for novel therapeutic tools in schizophrenia. Neonatal ventral hippocampus lesion (nVHL) in the rat has been extensively used to examine some of the pathophysiological mechanisms of schizophrenia since it mimics several behaviors, as well as abnormalities in morphological corticolimbic neurons. Thus, in this report, we determined the effects of the nVHL on locomotor behavior and memory in postpubertal rats. Also, we explored the density and the dynamics of the dendritic spines in the pyramidal neurons of layers 3 and 5 of the prefrontal cortex (PFC) and basolateral amygdala (BLA), and also in the nucleus accumbens (NAcc) medium spiny neurons (MSN). We found that nVHL rats have exhibited both hyperlocomotion and memory deficits. nVHL also reduced the number of dendritic spines and decreased the proportion of mature spines in these neurons. In conclusion, nVHL triggers behavioral abnormalities in postpubertal rats that can be associated not only with the lack of dendritic spines but also with distortion of these structures in corticolimbic neurons. Hence, the nVHL can be useful to explore the mechanisms of the dendritic spine pathology and its implications for schizophrenia.

Endoscopic Endonasal Transclival Approach for Resection of a Pontine Glioma: Surgical Planning, Surgical Anatomy, and Technique.

The endoscopic endonasal approach (EEA) has been proposed as a potential alternative for ventral brainstem lesions. The surgical anatomy, feasibility, and limitations of the EEA for intrinsic brainstem lesions are still poorly understood. To describe the surgical planning, anatomy, and technique of an intrinsic pontine glioma operated via EEA. Six-human brainstems were prepared for white matter microdissection. Ten healthy subjects were studied with high-definition fiber tractography (HDFT). A 56-yr-old female with right-hemiparesis underwent EEA for an exophytic pontine glioma. Pre- and postoperative HDFTs were implemented. The corticospinal tracts (CSTs) are the most eloquent fibers in the ventral brainstem. At the pons, CSTs run between the pontine nuclei and the middle cerebellar peduncle (MCP). At the lower medulla, the pyramidal decussation leaves no room for safe ventral access. In our illustrative case, preoperative HDFT showed left-CST displaced posteromedially and partially disrupted, right-CST posteriorly displaced, and MCP severely disrupted. A transclival exposure was performed achieving a complete resection of the exophytic component with residual intra-axial tumor. Immediately postop, patient developed new left-side abducens nerve palsy and worse right-hemiparesis. Ten days postop, her strength returned to baseline. HDFT showed preservation and trajectory restoration of the CSTs. The EEA provides direct access to the ventral brainstem, overcoming the limitations of lateral approaches. For intrinsic pathology, HDFT helps choosing the most appropriate surgical route/boundaries for safer resection. Further experience is needed to determine the indications and limitations of this approach that should be performed by neurosurgeons with high-level expertise in EEA.

The ipsilesional attention bias in right-hemisphere stroke patients as revealed by a realistic visual search task: Neuroanatomical correlates and functional relevance.

Objective: Right-hemisphere stroke may cause an ipsilesional attention bias and left hemispatial neglect. Computerized time-limited tasks are more sensitive than conventional paper–pencil tests in detecting these spatial attention deficits. However, their frequency in the acute stage of stroke, the neuroanatomical basis and functional relevance for patients’ everyday life are unclear. Method: A realistic visual search task is introduced, in which eye movements are recorded while the patient searches for paperclips among different everyday objects on a computer display. The “desk task” performance of 34 acute right-hemisphere stroke patients was compared to established paper–pencil tests for neglect and the Posner reaction time task, and finally correlated to structural brain lesions. Results: Most of the patients, even those without clinical neglect signs and with normal paper–pencil test performance, exhibited a clear ipsilesional attention bias in the desk task. This bias was highly correlated to the left-right asymmetry in the Posner task and to neglect-related functional impairment scores. Lesion-symptom mapping revealed task-specific differences: deficits in the desk task were associated with lesions of the superior temporal gyrus, contralesional unawareness in the Posner task with ventral frontal cortex lesions and paper–pencil cancellation bias with damage to the inferior parietal lobe. Neglect behavior was further associated with distinct frontoparietal white matter tract disconnections (inferior longitudinal fasciculus, superior longitudinal fasciculus, arcuate). Conclusions: Results from the novel desk task indicate a functional relevance of spatial attention deficits in right-hemisphere stroke patients, even if they are “subclinical.” This should be considered especially in patients without obvious clinical neglect signs.

Representation of Spatial and Feature Information in the Monkey Dorsal and Ventral Prefrontal Cortex

The primate prefrontal cortex (PFC) is critical for executive functions including working memory, task switching and response selection. The functional organization of this area has been a matter of debate over a period of decades. Early models proposed segregation of spatial and object information represented in working memory in the dorsal and ventral PFC, respectively. Other models emphasized the integrative ability of the entire PFC depending on task demands, not necessarily tied to working memory. An anterior-posterior hierarchy of specialization has also been speculated, in which progressively more abstract information is represented more anteriorly. Here we revisit this debate, updating these arguments in light of recent evidence in non-human primate neurophysiology studies. We show that spatial selectivity is predominantly represented in the posterior aspect of the dorsal PFC, regardless of training history and task performed. Objects of different features excite both dorsal and ventral prefrontal neurons, however neurons highly specialized for feature information are located predominantly in the posterior aspect of the ventral PFC. In accordance with neuronal selectivity, spatial working memory is primarily impaired by inactivation or lesion of the dorsal PFC and object working memory by ventral inactivation or lesion. Neuronal responses are plastic depending on task training but training too has dissociable effects on ventral and dorsal PFC, with the latter appearing to be more plastic. Despite the absence of an overall topography, evidence exists for the orderly localization of stimulus information at a sub-millimeter scale, within the dimensions of a cortical column. Unresolved questions remain, regarding the existence or not of a functional map at the areal and columnar scale, and the link between behavior and neuronal activity for different prefrontal subdivisions.

A Population-Based Model of the Temporal Memory in the Hippocampus.

Spatial and temporal dimensions are fundamental for orientation, adaptation, and survival of organisms. Hippocampus has been identified as the main neuroanatomical structure involved both in space and time perception and their internal representation. Dorsal hippocampus lesions showed a leftward shift (toward shorter durations) in peak-interval procedures, whereas ventral lesions shifted the peak time toward longer durations. We previously explained hippocampus lesion experimental findings by assuming a topological map model of the hippocampus with shorter durations memorized ventrally and longer durations more dorsal. Here we suggested a possible connection between the abstract topological maps model of the hippocampus that stored reinforcement times in a spatially ordered memory register and the “time cells” of the hippocampus. In this new model, the time cells provide a uniformly distributed time basis that covers the entire to-be-learned temporal duration. We hypothesized that the topological map of the hippocampus stores the weights that reflect the contribution of each time cell to the average temporal field that determines the behavioral response. The temporal distance between the to-be-learned criterion time and the time of the peak activity of each time cell provides the error signal that determines the corresponding weight correction. Long-term potentiation/depression could enhance/weaken the weights associated to the time cells that peak closer/farther to the criterion time. A coincidence detector mechanism, possibly under the control of the dopaminergic system, could be involved in our suggested error minimization and learning algorithm.

Risk Factor Analysis of Change in Intraoperative Neurophysiologic Monitoring During Cervical Open Door Laminoplasty

The aim of this study is to determine the risk factors affecting intraoperative neurophysiologic monitoring (IONM) changes, when such changes take place, and clinical outcomes associated with IONM change during cervical open door laminoplasty (COL) for cervical compressive myelopathy. Between 2010 and 2015, 79 patients who underwent COL with IONM recording were studied. Changes in motor evoked potentials or somatosensory evoked potentials over an alarm criterion were defined as IONM change. Patients with IONM change were assigned to the alarm group, and the others were classified as the control group. Baseline data and radiographic measurements were compared between the 2 groups. Radiologic parameters including maximal compression level (MCL), area and diameter of the spinal canal and ventral compressive lesion, stenosis grade, and occupying ratio of area (ORA) and length at the MCL were measured with magnetic resonance imaging. Thirteen patients were assigned to the alarm group and 66 patients were assigned to the control group. Multivariate analysis identified ORA at the MCL (odds ratio, 1.520; 95% confidence interval, 1.192-1.37; P= 0.001) as an independent risk factor for IONM change. Immediately after decompression, the IONM change occurred. One of 4 patients who did not fully recover from the IONM change had postoperative motor deficits. IONM change during COL occurred immediately after decompression, and a risk factor of IONM change was ORA at the MCL. If the IONM change was not fully recovered, a new motor deficit occurred after COL.

Preserved Object Weight Processing after Bilateral Lateral Occipital Complex Lesions.

Object interaction requires knowledge of the weight of an object, as well as its shape. The lateral occipital complex (LOC), an area within the ventral visual pathway, is well known to be critically involved in processing visual shape information. Recently, however, LOC has also been implicated in coding object weight before grasping-a result that is surprising because weight is a nonvisual object property that is more relevant for motor interaction than visual perception. Here, we examined the causal role of LOC in perceiving heaviness and in determining appropriate fingertip forces during object lifting. We studied perceptions of heaviness and lifting behavior in a neuropsychological patient (M.C.) who has large bilateral occipitotemporal lesions that include LOC. We compared the patient's performance to a group of 18 neurologically healthy age-matched controls. Participants were asked to lift and report the perceived heaviness of a set of equally weighted spherical objects of various sizes-stimuli which typically induce the size-weight illusion, in which the smaller objects feel heavier than the larger objects despite having identical mass. Despite her ventral stream lesions, M.C. experienced a robust size-weight illusion induced by visual cues to object volume, and the magnitude of the illusion in M.C. was comparable to age-matched controls. Similarly, M.C. evinced predictive fingertip force scaling to visual size cues during her initial lifts of the objects that were well within the normal range. These single-case neuropsychological findings suggest that LOC is unlikely to play a causal role in computing object weight.

Management of irreducible unilateral facet joint dislocations in subaxial cervical spine: two case reports and a review of the literature

BackgroundSkeletal and soft tissue damage are often associated with unilateral facet dislocations, which undoubtedly lead to instability of the spine and further increase difficulties in cervical reduction. This type of irreducible facet dislocation is usually accompanied with potential catastrophic consequences including neurological deficit and severe disability. Therefore, a consistent and evidence-based treatment plan is imperative.Case presentationThe literature regarding the management of traumatic unilateral locked cervical facet dislocations was reviewed. Two patient cases (a 30-year-old Asian man and a 25-year-old Asian woman) who suffered irreducible cervical facet dislocations were presented. These two patients received surgical treatments including posterior reduction by poking facet joints, adjacent spinous process fixation by wire rope banding, anterior plate fixation, and intervertebral fusion after the failure of skull traction and closed reduction. At the postoperative 24-month follow-up, intervertebral fusion was achieved and our patients’ neurological status improved based on the American Spinal Injury Association scale, compared with their preoperative status.ConclusionsUnilateral facet joint dislocations of subaxial cervical spine are difficult to reduce when complicated with posterior facet fractures or ligamentous injury. Magnetic resonance imaging can be beneficial for identifying ventral and dorsal compressive lesions, as well as ligamentous or capsule rupture. The combination of posterior reduction and anterior fixation with fusion has advantages in terms of clinical safety, ease of operation, and less iatrogenic damage.

Tratamiento Quirúrgico de los Meningiomas Espinales

Objetivo: Presentar nuestra experiencia en el tratamiento quirúrgico de los meningiomas espinales. Material y métodos: Estudio descriptivo retrospectivo que incluye a 24 pacientes operados de meningiomas espinales durante el período Julio de 2009 a Diciembre de 2016. Se analizaron datos epidemiológicos, antecedentes personales, sintomatología preoperatoria, características radiológicas, hallazgos intraoperatorios, grado de resección, descripción histológica y evolución post operatoria. Resultados: Se operaron 24 pacientes siendo 83% de sexo femenino. En cuanto a la localización, 79% fueron dorsales, 17% cervicales y 4% lumbares. La anatomía patológica reveló meningiomas grado I (OMS) en todos los casos. En el 63% se abordó la lesión por hemilaminectomía, logrando en éstas un grado de resección satisfactorio (Simpson 2). El 66% de los pacientes presentaron mejoría clínica post operatoria, 30% sin cambios significativos y solo un caso (4%) de empeoramiento. El periodo de seguimiento promedio fue de 14,9 meses. Conclusión: La cirugía continúa siendo el tratamiento de elección en los meningiomas espinales. El abordaje por hemilaminectomía es una opción útil en lesiones con base de implantación lateral. Lesiones predominantemente ventrales, con componente cálcico y alteraciones motoras preoperatorias suelen presentar mayor complejidad quirúrgica y peor evolución.

Extended endoscopic endonasal approach to the ventral skull base lesions

ObjectiveWith the use of multiple endoscopic endonasal surgical corridors, extended endoscopic endonasal approaches (EEEAs) are now being used to treat a wide range of ventral skull base lesions. Our aim was to present our experience with EEEAs to the ventral skull base lesions. Patients and MethodsThe study group consisted of 106 patients (57 men and 49 women) who underwent surgery for skull base lesions using EEEAs from 2010 to 2017. The EEEA was most commonly used for giant pituitary macroadenomas, sinonasal malignancies, cerebrospinal fluid (CSF) leaks, meningiomas, craniopharyngiomas, and fibro-osseous lesions. Four different approaches were used including transtuberculum-transplanum, transethmoidal-transcribriform, transclival, and transmaxillary-transpterygoidal. ResultsThe overall gross total resection (GTR) rate for these diverse pathologies was 75.0% in 88 patients (excluding the operations performed for non-neoplastic pathologies). GTR was achieved in 100%, 77.8%, 75%, 75%, 72.2%, 62.5%, 60% of fibro-osseous lesions, giant/large pitutary adenomas, meningiomas, esthesioneuroblastomas, sinonasal malignancies, craniopharyngiomas, and chordomas, respectively. The overall rate of improvement in visual fields was 86%. The overall rate of CSF leak was 8.4%. Other surgical complications included intracerebral hematoma and tension pneumocephalus. The mortality rate was 0.9%. ConclusionEEEA is a safe, well-tolerated and effective surgical treatment modality in the management of ventral skull base lesions. It should be performed with close interdisciplinary collaboration. Appropriate case selection is mandatory. However, despite improved reconstruction techniques, postoperative CSF leakage still remains a challenge.

Abnormalities in higher cortical visual processing

Normal visual processing includes signal stream from the retina via the lateral geniculate nucleus to the striate cortex Extra striate visual cortex performs the processings involving color and motion perception Thus the striate occipital lesions cause deficits affected the visual field while as extrastriate lesions cause deficits related to the perception of color and motion Extra striate cortical regions include ventral occipitotemporal and dorsal occipitoparietal streams Ventral stream lesions may produce defects such as agnosia prosopagnosia alexia and achromatopsia while dorsal stream lesions can cause akinetopsia and Balint syndrome Ophthalmologists have often difficulties in understanding the higher cortical visual deficits and so they usually ignore them The main purpose of this review article is to summarize the higher cortical and visual dysfunctions and to facilitate the understanding of these

Hyper-response to Novelty Increases c-Fos Expression in the Hippocampus and Prefrontal Cortex in a Rat Model of Schizophrenia.

Schizophrenia is a debilitating disorder that may have a neurodevelopmental origin. For this reason, animal models based on neonatal insults or manipulations have been extensively used to demonstrate schizophrenia-related behaviors. Among those, the neonatal ventral hippocampus lesion (nVHL) is largely used as a model of schizophrenia-related behavior as it mimics behavioral and neurochemical abnormalities often seen in schizophrenic patients including hyperlocomotion in a novel environment. To investigate the neuroanatomical basis of coding novelty in the nVHL rat, we assessed the behaviorallocomotor activity paradigm in a novel environment and measured expression of c-Fos, a marker of neural activation, in brain regions involved in the process of coding novelty or locomotion. Upon reaching adulthood, nVHL rats showed hyperlocomotion in the novel environment paradigm. Moreover, in nVHL rats the expression of c-Fos was greater in the prefrontal cortex (PFC) and CA1 regionof the dorsal hippocampus compared tosham rats. Whereas similar expression of c-Fos was observed in the basolateral amygdala, nucleus accumbens and dentate gyrusregion of hippocampus of nVHL and sham rats. These results suggest that the nVHL disrupts the neural activity in the PFC and CA1 region ofhippocampus in the process of coding novelty in the rat.

Ventral striatum lesions do not affect reinforcement learning with deterministic outcomes on slow time scales.

A large body of work has implicated the ventral striatum (VS) in aspects of reinforcement learning (RL). However, less work has directly examined the effects of lesions in the VS, or other forms of inactivation, on 2-armed bandit RL tasks. We have recently found that lesions in the VS in macaque monkeys affect learning with stochastic schedules but have minimal effects with deterministic schedules. The reasons for this are not currently clear. Because our previous work used short intertrial intervals, one possibility is that the animals were using working memory to bridge stimulus-reward associations from 1 trial to the next. In the present study, we examined learning of 60 pairs of objects, in which the animals received only 1 trial per day with each pair. The large number of object pairs and the long interval (approximately 24 hr) between trials with a given pair minimized the chances that the animals could use working memory to bridge trials. We found that monkeys with VS lesions were unimpaired relative to controls, which suggests that animals with VS lesions can still learn to select rewarded objects even when they cannot make use of working memory. (PsycINFO Database Record

Pituitary and skull-base lesions and the litigious patient.

The objective of this research was to evaluate litigation relating to the diagnosis and management of pituitary and ventral skull base lesions and delineate allegations involved in the decision to pursue medicolegal proceedings. Publically available federal and court records were accessed via the Westlaw Next database. Jury verdict and settlement reports relevant to pituitary and anterior skull-base lesions were accessed, and litigation was reviewed for alleged injuries, defendant specialty, patient demographics, and other factors raised in proceedings. Of 75 cases included, 50.7% were resolved in the defendant's favor. The most frequent physician specialties cited as defendants included primary care (20%), neurosurgery (17%), and radiology (16%), while otolaryngologists were defendants in only 5% of cases. Fifty-two (69%) did not involve surgical intervention; the most common allegations in these proceedings were misdiagnosis, permanent injury (19%), requiring additional procedures as a result of misdiagnosis (17%), permanent endocrine dysfunction (14%), and visual sequelae (12%). Among surgical cases, the most common allegations raised included permanent injury (17%), postoperative complications (14%), intraoperative complications (13%), and death (10%). Among cases resolved with payment, there was no statistical difference in payment between surgical cases ($5.7M) and nonsurgical cases ($4.8M). Misdiagnosis of endocrinopathy, failure to appropriately workup patients presenting with neurologic complaints, and radiologic misdiagnosis play important roles in the pursuit of litigation in nonsurgical cases. Sustaining permanent sequelae including endocrine and visual injury play an important role in surgical cases. Postoperative management appears to play just as important a role in the decision to pursue litigation as intraoperative considerations.

Endoscopic Endonasal Odontoidectomy with Anterior C1 Arch Preservation in Rheumatoid Arthritis: Long-Term Follow-Up and Further Technical Improvement by Anterior Endoscopic C1-C2 Screw Fixation and Fusion.

To examine the long-term outcomes (minimum of 4.5 years) of endoscopic endonasal odontoidectomy (EEO) with preservation of anterior C1 ring to treat irreducible ventral bulbo-medullary compressions in rheumatoid arthritis (RA) and to illustrate a novel technique of anterior pure endoscopic craniovertebral junction (CVJ) reconstruction and fusion. In fact, long-term clinical studies are still lacking to elucidate the effective role of EEO and whether it can obviate the need for posterior fixation. From November 2008 to January 2012, clinical and radiologic data of 7 patients presenting with RA and associated irreducible bulbo-medullary compression treated with EEO were analyzed retrospectively. In all patients, decompression was achieved by EEO with anterior C1 arch preservation. In the last 2 patients, after EEO, we used the spared anterior C1 arch for reconstruction of anterior column of CVJ by positioning, under pure endoscopic guidance, autologous bone and 2 tricortical screws between the anterior arch of C1 and the residual odontoid. All patients were examined clinically with Ranawat classification and radiographically with computed tomography, magnetic resonance imaging, and dynamic radiography immediately after surgery and during follow-up. Adequate bulbo-medullary decompression with anterior C1 arch preservation was obtained in all cases. At follow-up (average, 66.2 months; range, 51-91 months) all patients experienced an improvement at least of one Ranawat classification level and presented no clinical or radiologic signs of instability. EEO with anterior C1 arch sparing provides satisfying long-term results for irreducible ventral CVJ lesions in RA. The preservation of anterior C1 arch and, when possible, the reconstruction of anterior CVJ can prevent the need for posterior fusion.

Effects of Ventral Striatum Lesions on Stimulus-Based versus Action-Based Reinforcement Learning.

Learning the values of actions versus stimuli may depend on separable neural circuits. In the current study, we evaluated the performance of rhesus macaques with ventral striatum (VS) lesions on a two-arm bandit task that had randomly interleaved blocks of stimulus-based and action-based reinforcement learning (RL). Compared with controls, monkeys with VS lesions had deficits in learning to select rewarding images but not rewarding actions. We used a RL model to quantify learning and choice consistency and found that, in stimulus-based RL, the VS lesion monkeys were more influenced by negative feedback and had lower choice consistency than controls. Using a Bayesian model to parse the groups' learning strategies, we also found that VS lesion monkeys defaulted to an action-based choice strategy. Therefore, the VS is involved specifically in learning the value of stimuli, not actions.SIGNIFICANCE STATEMENT Reinforcement learning models of the ventral striatum (VS) often assume that it maintains an estimate of state value. This suggests that it plays a general role in learning whether rewards are assigned based on a chosen action or stimulus. In the present experiment, we examined the effects of VS lesions on monkeys' ability to learn that choosing a particular action or stimulus was more likely to lead to reward. We found that VS lesions caused a specific deficit in the monkeys' ability to discriminate between images with different values, whereas their ability to discriminate between actions with different values remained intact. Our results therefore suggest that the VS plays a specific role in learning to select rewarded stimuli.

Impaired peripheral reaching and on-line corrections in patient DF: Optic ataxia with visual form agnosia

An influential model of vision suggests the presence of two visual streams within the brain: a dorsal occipito-parietal stream which mediates action and a ventral occipito-temporal stream which mediates perception. One of the cornerstones of this model is DF, a patient with visual form agnosia following bilateral ventral stream lesions. Despite her inability to identify and distinguish visual stimuli, DF can still use visual information to control her hand actions towards these stimuli. These observations have been widely interpreted as demonstrating a double dissociation from optic ataxia, a condition observed after bilateral dorsal stream damage in which patients are unable to act towards objects that they can recognize. In Experiment 1, we investigated how patient DF performed on the classical diagnostic task for optic ataxia, reaching in central and peripheral vision. We replicated recent findings that DF is remarkably inaccurate when reaching to peripheral targets, but not when reaching in free vision. In addition we present new evidence that her peripheral reaching errors follow the optic ataxia pattern increasing with target eccentricity and being biased towards fixation. In Experiments 2 and 3, for the first time we examined DF's on-line control of reaching using a double-step paradigm in fixation-controlled and free-vision versions of the task. DF was impaired when performing fast on-line corrections on all conditions tested, similarly to optic ataxia patients. Our findings question the long-standing assumption that DF's dorsal visual stream is functionally intact and that her on-line visuomotor control is spared. In contrast, in addition to visual form agnosia, DF also has visuomotor symptoms of optic ataxia which are most likely explained by bilateral damage to the superior parietal-occipital cortex (SPOC). We thus conclude that patient DF can no longer be considered as an appropriate single-case model for testing the neural basis of perception and action dissociations.

Parkinsonism and dystonia are differentially induced by modulation of different territories in the basal ganglia

Numerous clinical and experimental observations suggest that deficient neuronal signaling in the globus pallidus externa (GPe) is integral to both Parkinson’s disease (PD) and dystonia. In our previous studies in jaundiced dystonic rats, widespread silencing of neurons in GP (rodent equivalent to GPe) preceded and persisted during dystonic motor activity. We therefore hypothesized that on a background of slow and highly irregular and bursty neuronal activity in GP, cortical motor drive produces profound inhibition of GP as the basis for action-induced dystonia in Gunn rats. Presently, the neurotoxin ibotenate was injected locally into the motor territory of GP at one to four sites, over one to two tracts, in 19 normal rats. We found that highly circumscribed dorsal motor territory lesions reproducibly induced parkinsonism, while ventral lesions consistently produced dystonia. Post-lesioning, slow neuronal burst oscillations in the entopeduncular nucleus distinguished parkinsonian from dystonic rats. Next, we compared the deep brain stimulation contact sites in the GP internus used to treat patients with PD (n=21 implants in 12 successive patients) versus dystonia (n=16 implants in nine patients) and found the efficacious territory for ameliorating PD to be located chiefly dorsal to that for dystonia. The comparative distribution for treating PD versus dystonia was therefore anatomically consistent with that for inducing these features via GP lesions in rodents. Our collective findings thus suggest that dystonia and parkinsonism are differentially produced by pathological silencing of GPe neurons along distinct motor sub-circuits, resulting in disparate pathological basal ganglia output signaling.