William Barnett Warrington (1869-1919).

William Barnett Warrington (1869-1919) was a physician and physiologist working in Liverpool, United Kingdom, at the end of the 19th and beginning of the 20th centuries. His training included periods at the National Hospital for the Paralysed and Epileptic, Queen Square, London, and in the Liverpool laboratory of Charles Scott Sherrington. He investigated structural alterations in nerve cells following various nerve lesions and helped to develop laboratory facilities to support clinical practice through the Pathological Diagnosis Society of Liverpool. His clinical interests were broad, but his main focus seems to have been in disorders of the peripheral nervous system. He published many papers, encompassing descriptions of Charcot-Marie-Tooth disease, brachial plexus paralyses (possibly including neuralgic amyotrophy), and, in the context of the First World War, traumatic peripheral nerve injuries. He may have described cases of Guillain-Barré syndrome prior to the eponymous description but despite being familiar with the technique of lumbar puncture, he did not report cerebrospinal fluid findings in these patients.

Facilitation of Fast Backward Priming After Left Cerebellar Continuous Theta-Burst Stimulation.

Traditional theories of backward priming account only for the priming effects found at long stimulus onset asynchronies (SOAs). Here, we suggest that the presence of backward priming at short SOAs may be related to the integrative role of the cerebellum. Previous research has shown that the right cerebellum is involved in forward associative priming. Functional magnetic resonance imaging reveals some activation of the left cerebellar hemisphere during backward priming; but what this activation represents is unclear. Here we explore this issue using continuous theta-burst transcranial magnetic stimulation (cTBS) and associative priming in a lexical decision task. We tested the hypothesis that the left cerebellum plays a role in backward priming and that this is dissociated from the role of the right cerebellum in forward priming. Before and after cTBS was applied to their left and right cerebellar hemispheres, participants completed a lexical decision task. Although we did not replicate the forward priming effect reported in the literature, we did find a significant increase in backward priming after left relative to right cerebellar cTBS. We consider how theories of cerebellar function in the motor domain can be extended to language and cognitive models of backward priming.

Cerebellar contributions to verbal working memory.

There is increasing evidence for a cerebellar role in working memory. Clinical research has shown that working memory impairments after cerebellar damage and neuroimaging studies have revealed task-specific activation in the cerebellum during working memory processing. A lateralisation of cerebellar function within working memory has been proposed with the right hemisphere making the greater contribution to verbal processing and the left hemisphere for visuospatial tasks. We used continuous theta burst stimulation (cTBS) to examine whether differences in post-stimulation performance could be observed based on the cerebellar hemisphere stimulated and the type of data presented. We observed that participants were significantly less accurate on a verbal version of a Sternberg task after stimulation to the right cerebellar hemisphere when compared to left hemisphere stimulation. Performance on a visual Sternberg task was unaffected by stimulation of either hemisphere. We discuss our results in the context of prior studies that have used cerebellar stimulation to investigate working memory and highlight the cerebellar role in phonological encoding.

Impaired visuospatial transformation but intact sequence processing in Parkinson disease.

OBJECTIVE: We examined whether visuospatial deficits in Parkinson disease (PD) can be explained by a domain-general, nonspatial impairment in the sequencing or serial chaining of mental operations. BACKGROUND: PD has been shown to be associated with impaired visuospatial processing, but the mechanisms of this impairment remain unclear. METHODS: Thirteen patients with PD and 20 age-matched, neurologically normal controls performed a visuospatial grid navigation task requiring sequential spatial transformations. The participants also performed a control task of serial number subtraction designed to assess their nonvisuospatial sequencing. The tasks were matched in structure and difficulty. RESULTS: The patients were impaired on the visuospatial task but not in serial number subtraction. This finding suggests that visuospatial processing impairments in PD do not derive from a general impairment affecting sequencing or serial chaining. CONCLUSIONS: We argue that visuospatial deficits in PD result from impairments to spatial transformation routines involved in the computation of mappings between spatial locations. These routines are mediated by dopaminergic pathways linking the basal ganglia, prefrontal cortex, supplementary motor area, and parietal cortex.

Challenges of proper placebo control for non-invasive brain stimulation in clinical and experimental applications.

A range of techniques are now available for modulating the activity of the brain in healthy people and people with neurological conditions. These techniques, including transcranial magnetic stimulation (TMS) and transcranial current stimulation (tCS, which includes direct and alternating current), create magnetic or electrical fields that cross the intact skull and affect neural processing in brain areas near to the scalp location where the stimulation is delivered. TMS and tCS have proved to be valuable tools in behavioural neuroscience laboratories, where causal involvement of specific brain areas in specific tasks can be shown. In clinical neuroscience, the techniques offer the promise of correcting abnormal activity, such as when a stroke leaves a brain area underactive. As the use of brain stimulation becomes more commonplace in laboratories and clinics, we discuss the safety and ethical issues inherent in using the techniques with human participants, and we suggest how to balance scientific integrity with the safety of the participant.

Feature integration in visual working memory: parietal gamma activity is related to cognitive coordination.

The mechanism by which distinct subprocesses in the brain are coordinated is a central conundrum of systems neuroscience. The parietal lobe is thought to play a key role in visual feature integration, and oscillatory activity in the gamma frequency range has been associated with perception of coherent objects and other tasks requiring neural coordination. Here, we examined the neural correlates of integrating mental representations in working memory and hypothesized that parietal gamma activity would be related to the success of cognitive coordination. Working memory is a classic example of a cognitive operation that requires the coordinated processing of different types of information and the contribution of multiple cognitive domains. Using magnetoencephalography (MEG), we report parietal activity in the high gamma (80-100 Hz) range during manipulation of visual and spatial information (colors and angles) in working memory. This parietal gamma activity was significantly higher during manipulation of visual-spatial conjunctions compared with single features. Furthermore, gamma activity correlated with successful performance during the conjunction task but not during the component tasks. Cortical gamma activity in parietal cortex may therefore play a role in cognitive coordination.

Functional network topology in drug resistant and well-controlled idiopathic generalized epilepsy: a resting state functional MRI study.

Despite an increasing number of drug treatment options for people with idiopathic generalized epilepsy (IGE), drug resistance remains a significant issue and the mechanisms underlying it remain poorly understood. Previous studies have largely focused on potential cellular or genetic explanations for drug resistance. However, epilepsy is understood to be a network disorder and there is a growing body of literature suggesting altered topology of large-scale resting networks in people with epilepsy compared with controls. We hypothesize that network alterations may also play a role in seizure control. The aim of this study was to compare resting state functional network structure between well-controlled IGE (WC-IGE), drug resistant IGE (DR-IGE) and healthy controls. Thirty-three participants with IGE (10 with WC-IGE and 23 with DR-IGE) and 34 controls were included. Resting state functional MRI networks were constructed using the Functional Connectivity Toolbox (CONN). Global graph theoretic network measures of average node strength (an equivalent measure to mean degree in a network that is fully connected), node strength distribution variance, characteristic path length, average clustering coefficient, small-world index and average betweenness centrality were computed. Graphs were constructed separately for positively weighted connections and for absolute values. Individual nodal values of strength and betweenness centrality were also measured and 'hub nodes' were compared between groups. Outcome measures were assessed across the three groups and between both groups with IGE and controls. The IGE group as a whole had a higher average node strength, characteristic path length and average betweenness centrality. There were no clear differences between groups according to seizure control. Outcome metrics were sensitive to whether negatively correlated connections were included in network construction. There were no clear differences in the location of 'hub nodes' between groups. The results suggest that, irrespective of seizure control, IGE interictal network topology is more regular and has a higher global connectivity compared to controls, with no alteration in hub node locations. These alterations may produce a resting state network that is more vulnerable to transitioning to the seizure state. It is possible that the lack of apparent influence of seizure control on network topology is limited by challenges in classifying drug response. It is also demonstrated that network topological features are influenced by the sign of connectivity weights and therefore future methodological work is warranted to account for anticorrelations in graph theoretic studies.

Unitary haptic perception: integrating moving tactile inputs from anatomically adjacent and non-adjacent digits.

How do we achieve unitary perception of an object when it touches two parts of the sensory epithelium that are not contiguous? We investigated this problem with a simple psychophysical task, which we then used in an fMRI experiment. Two wooden rods were moved over two digits positioned to be spatially adjacent. The digits were either from one foot (or hand) or one digit was from either foot (or hand). When the rods were moving in phase, one object was reliably perceived. By contrast, when the rods were moving out of phase, two objects were reliably perceived. fMRI revealed four cortical areas where activity was higher when the moving rods were perceived as one object relative to when they were perceived as two separate objects. Areas in the right inferior parietal lobule, the left inferior temporal sulcus and the left middle frontal gyrus were activated for this contrast regardless of the anatomical configuration of the stimulated sensory epithelia. By contrast, the left intraparietal sulcus was activated specifically when integration across the midline was required, irrespective of whether the stimulation was applied to the hands or feet. These results reveal a network of brain areas involved in generating a unified percept of the presence of an object that comes into contact with different parts of the body surface.

Are faces special? A case of pure prosopagnosia.

The ability to recognize individual faces is of crucial social importance for humans and evolutionarily necessary for survival. Consequently, faces may be "special" stimuli, for which we have developed unique modular perceptual and recognition processes. Some of the strongest evidence for face processing being modular comes from cases of prosopagnosia, where patients are unable to recognize faces whilst retaining the ability to recognize other objects. Here we present the case of an acquired prosopagnosic whose poor recognition was linked to a perceptual impairment in face processing. Despite this, she had intact object recognition, even at a subordinate level. She also showed a normal ability to learn and to generalize learning of nonfacial exemplars differing in the nature and arrangement of their parts, along with impaired learning and generalization of facial exemplars. The case provides evidence for modular perceptual processes for faces.

A tale of two agnosias: distinctions between form and integrative agnosia.

The performance of two patients with visual agnosia was compared across a number of tests examining visual processing. The patients were distinguished by having dorsal and medial ventral extrastriate lesions. While inanimate objects were disadvantaged for the patient with a dorsal extrastriate lesion, animate items are disadvantaged for the patient with the medial ventral extrastriate lesion. The patients also showed contrasting patterns of performance on the Navon Test: The patient with a dorsal extrastriate lesion demonstrated a local bias while the patient with a medial ventral extrastriate lesion had a global bias. We propose that the dorsal and medial ventral visual pathways may be characterized at an extrastriate level by differences in local relative to more global visual processing and that this can link to visually based category-specific deficits in processing.

Aortic dissection presenting as uniocular blindness.

A patient presented with uniocular blindness and headache, which was initially suspected to be subarachnoid hemorrhage. The patient had a seven-year history of diabetes mellitus, hypertension and hypothyroidism, as well as a two-year history of congestive cardiac failure with aortic regurgitation. Upon autopsy, the patient was diagnosed with aortic dissection. There are no other known reports of such a presentation. This case demonstrates that aortic dissection can present without any classical features, and hence it is important to consider the possibility of dissection in patients with long-standing hypertension and acute neurologic symptoms associated with pain.

Does transcranial direct current stimulation to prefrontal cortex affect mood and emotional memory retrieval in healthy individuals?

Studies using transcranial direct current stimulation (tDCS) of prefrontal cortex to improve symptoms of depression have had mixed results. We examined whether using tDCS to change the balance of activity between left and right dorsolateral prefrontal cortex (DLPFC) can alter mood and memory retrieval of emotional material in healthy volunteers. Participants memorised emotional images, then tDCS was applied bilaterally to DLPFC while they performed a stimulus-response compatibility task. Participants were then presented with a set of images for memory retrieval. Questionnaires to examine mood and motivational state were administered at the beginning and end of each session. Exploratory data analyses showed that the polarity of tDCS to DLPFC influenced performance on a stimulus-response compatibility task and this effect was dependent on participants' prior motivational state. However, tDCS polarity had no effect on the speed or accuracy of memory retrieval of emotional images and did not influence positive or negative affect. These findings suggest that the balance of activity between left and right DLPFC does not play a critical role in the mood state of healthy individuals. We suggest that the efficacy of prefrontal tDCS depends on the initial activation state of neurons and future work should take this into account.

Cerebellar contributions to spatial memory.

There is mounting evidence for a role for the cerebellum in working memory (WM). The majority of relevant studies has examined verbal WM and has suggested specialisation of the right cerebellar hemisphere for language processing. Our study used theta burst stimulation (TBS) to examine whether there is a converse cerebellar hemispheric specialisation for spatial WM. We conducted two experiments to examine spatial WM performance before and after TBS to mid-hemispheric and lateral locations in the posterior cerebellum. Participants were required to recall the order of presentation of targets on a screen or the targets' order of presentation and their locations. We observed impaired recollection of target order after TBS to the mid left cerebellar hemisphere and reduced response speed after TBS to the left lateral cerebellum. We suggest that these results give evidence of the contributions of the left cerebellar cortex to the encoding and retrieval of spatial information.

Brain stimulation studies of non-motor cerebellar function: a systematic review.

Evidence for a cerebellar role in non-motor functions has been demonstrated by clinical and neuroimaging research. These approaches do not allow causal relationships to be inferred though the experimental manipulation of the cerebellum. Transcranial magnetic and current stimulation may allow better understanding of the cerebellum via the temporary alteration of its operation in healthy volunteers. This review examined all studies of the cerebellar role in non-motor functions using non-invasive brain stimulation. Of 7585 papers captured by an initial search, 26 met specific selection criteria. Analysis revealed behavioural effects across learning, memory, cognition, emotional processing, perception and timing, though the results were not sufficiently similar as to offer a definitive statement of the cerebellum's role. The non-invasive application of stimulation to the cerebellum presents challenges due to surrounding anatomy and the relatively small target areas involved. This review analysed the methods used to address these challenges with a view to suggesting methodological improvements for the establishment of standards for the location of cerebellar stimulation targets and appropriate levels of stimulation.

Visuospatial transformation impairments in Parkinson's disease.

Some previous studies have reported impairments in Parkinson's disease (PD) that affect performance on visuospatial tasks. The aim of this study was to further elucidate the underlying cognitive impairment to visuospatial processing in PD. Nondementing PD patients and neurologically normal, age-matched controls completed two tasks of visuospatial transformation. In Task 1, observers made perceptual matching judgments about the shape equivalence of two upright or rotated 2D novel patterns. Task 2 used a recognition memory paradigm in which participants first memorized a target object at a specific orientation and then made target/nontarget judgments to targets or visually similar distractors at varying orientations. Analyses of the regression slopes between response times and angular disparity showed that PD is associated with impairments affecting spatial transformation during image normalization in both tasks. The results also showed that the patients were more impaired, relative to controls, at spatial transformation during the perceptual matching of two images, than in the recognition memory task. It is suggested that PD can result in deficits affecting spatial transformation processes that are modulated by working memory and task demands.

Active collisions in altered gravity reveal eye-hand coordination strategies.

Most object manipulation tasks involve a series of actions demarcated by mechanical contact events, and gaze is usually directed to the locations of these events as the task unfolds. Typically, gaze foveates the target 200 ms in advance of the contact. This strategy improves manual accuracy through visual feedback and the use of gaze-related signals to guide the hand/object. Many studies have investigated eye-hand coordination in experimental and natural tasks; most of them highlighted a strong link between eye movements and hand or object kinematics. In this experiment, we analyzed gaze strategies in a collision task but in a very challenging dynamical context. Participants performed collisions while they were exposed to alternating episodes of microgravity, hypergravity and normal gravity. First, by isolating the effects of inertia in microgravity, we found that peak hand acceleration marked the transition between two modes of grip force control. Participants exerted grip forces that paralleled load force profiles, and then increased grip up to a maximum shifted after the collision. Second, we found that the oculomotor strategy adapted visual feedback of the controlled object around the collision, as demonstrated by longer durations of fixation after collision in new gravitational environments. Finally, despite large variability of arm dynamics in altered gravity, we found that saccades were remarkably time-locked to the peak hand acceleration in all conditions. In conclusion, altered gravity allowed light to be shed on predictive mechanisms used by the central nervous system to coordinate gaze, hand and grip motor actions during a mixed task that involved transport of an object and high impact loads.

Haptic and visual influences on grasp point selection.

When using precision grip to pick up objects, there are many possible pairs of grasp points that permit the thumb and index finger to exert opposed forces for secure grip. Previously, it was shown that individuals select grasp points so that the line between them (grasp axis) passes through or near the center of mass (CoM), thus minimizing the torque around the grasp axis during lifting. The accuracy of grasp axis selection depended on object spatial symmetry, indicating the importance of vision. The authors investigated how grasp point selection is influenced by haptic as well as visual information. Ten participants lifted cuboids whose CoM was located either symmetrically in the geometric center or asymmetrically toward one end. Results for the asymmetric cuboid revealed that grasp points migrated toward the asymmetric CoM from the geometric center. This was more pronounced in the presence of visual cues that reliably indicated the location of CoM. The results suggest that grasp point selection is influenced by a multimodal representation of CoM.

Olfactory Examination in Korsakoff's Syndrome: Implications for Early Diagnosis.

Whilst olfactory dysfunction has been reported in Korsakoff's Syndrome (KS) patients, the diagnostic implications of this have not been fully explored. KS can be difficult to diagnose because cognitive symptoms are similar to other diagnoses. For instance, patients with Frontal Lobe (FL) Syndrome may present with memory impairments that are similar to KS. Participants were given the Benton Visual Retention Test-Fifth Edition (BVRT-V), to identify working memory dysfunction, and a Brief Smell Identification Test (B-SIT), to evaluate olfactory function. B-SIT scores were found to be significantly lower in the KS group compared to the control and FL groups. In contrast, the error scores on the BVRT-V were significantly higher in both the KS and FL groups compared to the healthy control subjects. Therefore, we suggest that olfactory function may aid in the differential diagnosis of patients presenting with working memory dysfunction.

Hemispheric specialisation in haptic processing.

This study investigated the organising principles of touch. We examined specialisations within the haptic system and their hemispheric distribution. Haptic processing consists of the integration of data from multiple sources to form a single percept. Previous research provides strong support for a hierarchical and functional distribution within haptic processing. We investigated hemispheric asymmetry in haptic discrimination of objects with differing textures and centres of mass. By analogy with vision it was hypothesised that participants would demonstrate a left-hand advantage for centre of mass discrimination (a 'global', presumed right hemisphere, judgement) and a right-hand advantage for surface texture judgements (a 'local', presumed left hemisphere discrimination). We found that left-handed participants showed these effects to a lesser degree than did the right-handers, consistent with the notion that left-handed people generally show weaker asymmetries in bimanual tasks. In a second experiment the effect of conflicting information on haptic percept formation was investigated. Following from the previous hypotheses it was predicted that participants would be more accurate with their right hands at judging conflicting surfaces. Contrary to predictions an advantage was demonstrated for the left hand for texture discrimination and for the right hand for centre of mass judgement.