Effects of lesions to area V6A in monkeys

In order to assess the role played by area V6A in visuomotor control, two adult green monkeys ( Cercopithecus aethiops) were subjected to small, bilateral lesions in the anterior bank of the parieto-occipital sulcus. Before and after the lesions, monkeys were tested for naturally designed reaching, grasping and picking-up pieces of food from various positions on a plate and from a differently oriented narrow slit. All movements were recorded with closed circuit TV and analysed offline on a single-photogram basis for defective reaching and wrist orientation. V6A lesions provoked parietal weakness, reluctance to move, and specific deficits in reaching, wrist orientation and grasping. Recovery from the observed deficits was rapid, even after a second, contralateral lesion was given, creating a bilateral lesion. Thus, together with previous anatomical and electrophysiological data, these results directly support the hypothesis that area V6A is part of the network involved in the control of reaching movements and wrist orientation.     

Effects of posterior parietal lesions (area 7) on VOR in monkeys

Summary Unilateral ablations of area 7 were performed in three adult monkeys. Vestibulo-ocular reflex (VOR) was tested in the dark by sinusoidal rotations at different frequencies. Following lesion of area 7, spontaneous nystagmus was observed in the dark, with the fast phase directed toward the lesioned side. The same lesion induced a strong VOR asymmetry due to a gain decrease when the animal was rotated toward the side contralateral to the lesion and an increase when rotated toward the opposite side. These VOR deficits were transient: spontaneous nystagmus was no longer present after the first post-operative week whereas the VOR asymmetry lasted for 2 to 4 weeks after the lesion. It is concluded that area 7 might be involved in an ipsilateral control of the slow component of VOR. These results support the idea that posterior parietal cortex plays a role in body reference stabilization.     

A quantitative analysis of stimulus- and movement-related responses in the posterior parietal cortex of the monkey

Summary The posterior parietal cortex (areas 5 and 7) in monkeys has been described as a higher association cortex and as such, area 5 has been attributed a complex somaesthetic function. More recently, a role in the formation of motor commands has been postulated for these two cortical areas. We have been particularly interested in the role area 5 neurons may have in movement initiation. Single neuron activity was recorded in area 5 during the performance of a trained forelimb movement in monkeys and neuronal responses which occurred prior to movement were observed. In the present report, we have examined the neuronal discharge data trial by trial using a technique of data analysis which enabled us to separate the changes in neuronal activity into stimulus- or movement-related responses. Both stimulus- and movement-related responses were identified. The stimulus-related responses were not simple sensory responses since they were also influenced by the timing of the onset of movement. These results suggest that certain area 5 neurons may be involved in the linking of sensory inputs with motor outputs. Cerebrocerebellar loops may be a pathway in this linkage. The latencies of the movement-related responses were such that corollary discharge from the motor cortex may have played a role in this activity. Such corollary discharge may be a form of information used by the animal to execute movement in the absence of peripheral feedback.     

Inactivation of macaque lateral intraparietal area delays initiation of the second saccade predominantly from contralesional eye positions in a double-saccade task

Previous studies have shown that, although lateral intraparietal (LIP) area neurons have retinotopic receptive fields, the response strength of these cells is modulated by eye position. This combining of retinal and eye position information can form a distributed coding of target locations in a head-centered coordinate frame. Such an implicit head-centered coding offers one mechanism for maintaining spatial stability across eye movements and can be used to compute new oculomotor error vectors after each eye movement. An alternative mechanism is to use eye displacement signals rather than eye position signals to maintain spatial stability. The aim of this study was to distinguish which of these two extra-retinal signals (or perhaps both signals) are employed in a double saccade task, which required the monkey to use extraretinal information associated with the first saccade to localize a remembered target for a second saccade. By varying the direction and the end point of the first saccade and selectively inactivating area LIP in one hemisphere with muscimol injection, we were able to distinguish between the two mechanisms by observing how the second saccade was impaired in this task. The displacement mechanism predicts that, if the first saccade is in the contralesional direction, the second saccade will be impaired, and the end point of the first saccade would not be important. The eye position mechanism predicts that if the first saccade ended in the contralesional head-centered space, the second saccade will be impaired, no matter in which direction the first saccade is made. Results showed that, after area LIP lesion, when the first saccade stepped into the contralesional field, the error rate of the second saccade became higher and the latency longer. However, when the end point of the first saccade was constant, the direction of the first saccade had much less effect on the second saccade. These results suggest that eye position, and not eye displacement, is the more predominant factor in this task. In a different behavioral paradigm, the monkeys performed single visual and memory saccades from different initial eye positions. It was found that the impairment of either the metrics or dynamics of visual and memory saccades did not significantly vary with the different eye positions. It thus appears that the performance of single visual and memory saccades is best described in an oculocentric coordinate frame that does not rely on extraretinal signals. Altogether these results lend further support to the hypothesis that, by combining retinal and eye position signals, area LIP contains concurrent eye-centered and head-centered representations of the visual space. Depending on the task, either representation can be used.     

Properties of spike train spectra in two parietal reach areas

In the lateral intraparietal area (LIP), a saccade-related region of the posterior parietal cortex (PPC), spiking activity recorded during the memory period of an instructed-delay task exhibits temporal structure that is spatially tuned. These results provide evidence for the existence of 'dynamic memory fields' which can be read-out by other brain areas, along with information contained in the mean firing rate, to give the direction of a planned movement. We looked for evidence of dynamic memory fields in spiking activity in two parietal reach areas, the parietal reach region (PRR) and area 5. Monkeys made center-out reaches to eight target locations in an instructed-delay task with a memory component. Neurons in both areas exhibited sustained activity during the delay period that was spatially tuned. Many single cell PRR spectra exhibited spatially tuned temporal structure, as evidenced by a significant and spatially tuned peak in the 20–50 Hz band. The PRR population spectrum of spike trains was also tuned, with the peak power centered on approximately 25 Hz. In contrast, area 5 spiking activity did not exhibit any significant temporal structure. These results suggest that different mechanisms underlie sustained delay period activity in these two areas and that dynamic memory fields, as revealed by our techniques, are more prominent in PRR than in area 5. Temporal structure in the spike train and local field potential (LFP) are related in at least one other brain area (LIP). The present results suggest then that LFP activity obtained from PRR may be better suited than area 5 LFP activity for use in neural prosthetic systems that incorporate analysis of temporal structure as part of a decode mechanism for extracting intended movement goals.     

Transcranial magnetic stimulation to right parietal cortex modifies the attentional blink

The attentional blink (AB) reflects a limitation in the ability to identify multiple items in a stream of rapidly presented information. Repetitive transcranial magnetic stimulation (rTMS), applied to a site over the right posterior parietal cortex, reduced the magnitude of the AB to visual stimuli, whilst no effect of rTMS was found when stimulation took place at a control site. The data confirm that the posterior parietal cortex may play a critical role in temporal as well as spatial aspects of visual attention.     

Impact of repetitive transcranial magnetic stimulation of the parietal cortex on metabolic brain activity: a<Superscript> 14</Superscript>C-2DG tracing study in the cat

Transcranial magnetic stimulation (TMS) is increasingly utilized in clinical neurology and neuroscience. However, detailed knowledge of the impact and specificity of the effects of TMS on brain activity remains unresolved. We have used ¹⁴C-labeled deoxyglucose (¹⁴C-2DG) mapping during repetitive TMS (rTMS) of the posterior and inferior parietal cortex in anesthetized cats to study, with exquisite spatial resolution, the local and distant effects of rTMS on brain activity. High-frequency rTMS decreases metabolic activity at the primary site of stimulation with respect to homologue areas in the unstimulated hemisphere. In addition, rTMS induces specific distant effects on cortical and subcortical regions known to receive substantial efferent projections from the stimulated cortex. The magnitude of this distal impact is correlated with the strength of the anatomical projections. Thus, in the anesthetized animal, the impact of rTMS is upon a distributed network of structures connected to the primary site of application.B.R. Payne has passed away since this paper was completed.     

Opposite impact on <Superscript>14</Superscript>C-2-deoxyglucose brain metabolism following patterns of high and low frequency repetitive transcranial magnetic stimulation in the posterior parietal cortex

Repetitive transcranial magnetic stimulation (rTMS) appears capable of modulating human cortical excitability beyond the duration of the stimulation train. However, the basis and extent of this “off-line” modulation remains unknown. In a group of anesthetized cats, we applied patterns of real or sham focal rTMS to the visuo-parietal cortex (VP) at high (HF) or low (LF) frequency and recorded brain glucose uptake during (on-line), immediately after (off-line), or 1 h after (late) stimulation. During the on-line period LF and HF rTMS induced a significant relative reduction of ¹⁴C-2DG uptake in the stimulated VP cortex and tightly linked cortical and subcortical structures (e.g. the superficial superior colliculus, the pulvinar, and the LPl nucleus) with respect to homologue areas in the unstimulated hemisphere. During the off-line period HF rTMS induced a significant relative increase in ¹⁴C-2DG uptake in the targeted VP cortex, whereas LF rTMS generated the opposite effect, with only mild network impact. Moderate distributed effects were only recorded after LF rTMS in the posterior thalamic structures. No long lasting cortical or subcortical effects were detected during the late period. Our findings demonstrate opposite modulation of rTMS on local and distant effects along a specific network, depending on the pattern of stimulation. Such effects are demonstrated in the anesthetized animal, ruling out behavioral and non-specific reasons for the differential impact of the stimulation. The findings are consistent with previous differential electrophysiological and behavioral effects of low and high frequency rTMS patterns and provide support to uses of rTMS in neuromodulation. ^†Prof. Payne passed away in May 2004. This article is submitted in his memory.     

Electrophysiological study of prefrontal neurones of cats during a motor task

 The prefrontal cortex is involved in many processes, some of which are related to motor activity such eye movements and speech. Experimental data exist that suggest that prefrontal cortical activity occurs in relation to attention, short-term memory, affective discrimination, and complex forms of motor behaviour, i.e. anticipatory preparation, motor sequences, programming of speech, etc. We were interested in studying participation of this cortical region in locomotion. For this purpose, recordings were made of unitary activity in the prefrontal cortex of chronically prepared cats walking on an exercise belt that was moving at a speed of 0.1 m/s. From a total of 63 neurones in the prefrontal area from which recordings were made, 37 (59%) changed their activity during locomotion, 28 of which (76%) increased and 9 of which (24%) decreased their frequency of discharge; the remaining 26 units (41%) showed no locomotor-related change in activity. The results obtained show that 59% of prefrontal units are involved in the locomotor process and it is reasonable to assume that their activity contributes to the control of the movements. Received: 24 October 1996 / Received after revision: 23 January 1997 / Accepted: 4 February 1997     

Projections of the temporo-parietal cortex on vestibular complex in the macaque monkey (Macaca fascicularis)

Summary Connections of the posterior parietal cortex (area 7) with the vestibular complex have been studied in 4 macaque monkeys by anterograde axonal transport methods. WGA-HRP and tritiated amino-acids have been injected in the posterior part of area 7 including the caudal end of the superior bank of superior temporal sulcus and the lateral sulcus. Labeled terminals were observed in the vestibular nuclei complex and distributed bilaterally with a greater ipsilateral contribution. Two main groups of area 7 efferences were found to project to vestibular complex: a) A first group terminates on vestibular nuclei (the inferior vestibular nucleus and the caudal part of the medial nucleus) mainly connected with cerebello-spinal system, b) A second group terminates on vestibular nuclei (the medial and the superior vestibular nuclei and the y group) mainly involved in vestibulo-ocular mechanisms. The prepositus hypoglossi nucleus has also been found to receive area 7 projections. It is concluded that the possible control played by area 7 on the vestibulo-ocular reflex might be exerted through these direct cortico-vestibular projections.     

Individual variation in the location of the parietal eye fields: a TMS study

Transcranial magnetic stimulation (TMS) is a popular technique that can be used to investigate the functional role of specific cortical areas with reference to a particular behavioural task. Single-cell recording studies performed in non-human primates have demonstrated that a region of the parietal lobe known as the lateral intraparietal area is specialized in the planning and control of saccadic eye movements. The homologue of this area in humans is termed the parietal eye fields (PEF) and its role in relation to saccades has previously been examined using TMS. In this paper individual variability in the functional effect of parietal TMS on the latency, amplitude and angular direction of visually-guided saccades has been assessed. By examining individual variability in the spatial distribution of scalp-based localization and brain surface anatomy and stereotaxic localizations of the PEF it was shown that the distances between the sites determined by these three methods were not negligible, which raises problems regarding the most reliable anatomical localization technique to use. An assessment of the effect of TMS on saccade metrics (latency, amplitude error and angular error) at a grid of locations over parietal cortex demonstrated a large amount of intra-individual variability in the site where TMS had most affected saccades, leading to the conclusion that there is individual variability in the functional effects of parietal TMS on saccade planning and execution. This study confirms the idea that it may be problematic to use a fixed scalp location for every participant in a study. It may in fact be more appropriate to determine TMS sites functionally on an individual basis if possible. This finding may guide further studies using TMS and saccade planning in order to optimize their capability to investigate this area and to draw meaningful biological conclusions.     

Activation of brain regions using task-state FMRI in patients with mild traumatic brain injury: a meta-analysis

Activation likelihood estimation meta-analysis was performed to examine the activation characteristics of cognition-related brain regions in patients with mild traumatic brain injury (mTBI). The databases PubMed, Ovid, Cochrane Library, Google Scholar, CNKI, WFSD, and VIP were systematically searched. The software Ginger-ALE 3.0.2 was used for coordinate unification and meta-analysis. Seven studies with a total of 314 subjects were included. Meta-analysis results indicated that compared with healthy subjects, mTBI patients had enhanced activation in the left anterior angular gyrus, left occipital joint visual, left midbrain, right temporal angular gyrus, right cerebellar tonsil, left frontal insula, and right inferior frontal gyrus. mTBI patients had attenuated activation in the right dorsolateral prefrontal lobe, left cerebellar anterior lobe, left dorsolateral prefrontal lobe, right middle frontal gyrus, right posterior cingulate gyrus, left joint visual, left supramarginal gyrus, left middle frontal gyrus, right precuneus, left dorsolateral prefrontal cortex, right frontal eye field, right lower parietal gyrus, corpus callosum, right frontal pole region, and left prefrontal lobe. Further joint analysis revealed that the dorsolateral prefrontal lobe of the right middle frontal gyrus was a region of attenuated co-activation. The dorsolateral prefrontal lobe of the right middle frontal gyrus showing attenuated activation was the main brain region distinguishing mTBI patients from healthy subjects. Cognitive deficits could be associated with attenuated activation in the dorsolateral prefrontal lobe of the right middle frontal gyrus, which could be due to a decline in the recruitment ability of the neural network involved in controlling attention.     

Pre-movement activity of neurons in the parietal associative cortex of the cat during different types of voluntary movement

Pre-movement activation of electromyographic spike activity of 201 neurons of field 5 was studied in cats trained to carry out a stereotypical act (lifting the anterior footpad to press a pedal) in response to a conditioned stimulus (experimental series 1) and without a conditioned stimulus (self-initiated movement, experimental series 2). In series 1, 69.2% of neurons were activated and 13.5% were inhibited before the movement. Prior changes in activity were also seen in intersignal movements, with activation of 40.6% and inhibition of 21.7% of neurons. The time parameters of excitatory and inhibitory responses in both situations were similar, with pre-movement intervals of 19-1640 msec. In series 2, pre-movement inhibition was seen rather more frequently than activation (36.7% and 33.7% respectively). The earliest changes were inhibitory, occurring some 1800 msec before movements, while excitatory changes occurred only 880 msec before movement. These data indicate the involvement of the parietal associative area in the cat not only in executing, but also in preparing for different types of movement, including self-initiated movements, and that inhibition has an active role in this process. Department of Human and Animal Physiology and Biophysics (Director V. G. Sidyakin), Simferopol State University. Translated from Fiziologicheskii Zhurnal im. I. M. Sechenova, Vol. 81, No. 4, pp. 70–75, April, 1995.     

Executive control over response priming and conflict: a transcranial magnetic stimulation study

In the present study repetitive transcranial magnetic stimulation (rTMS) was utilised to interrupt neural activity in selected cortical areas at several different time periods while participants performed a stimulus-response correspondence (SRC) task. Responses are usually faster and less error-prone when stimulus (S) and response (R) features correspond than when they do not. Dual-route models of response preparation account for such SRC effects by postulating an indirect route performing S-R selection and a parallel direct route where S features prime their corresponding responses. SRC effects have recently been shown to depend on the preceding trial type, that is, SRC effects are largely reduced when preceded by a non-corresponding trial as compared to a preceding corresponding trial. Present results show that this context dependency of the SRC effect was hindered when rTMS was applied to the left dorsolateral prefrontal cortex (DLPFC) 500-300 ms before the onset of the next trial. Moreover, the SRC effect was reduced overall when applying rTMS volleys to the right posterior parietal cortex (PPC) for 200 ms with the onset of the visual stimulus. We conclude that the left DLPFC is involved in the context-dependent control of response conflicts, whereas the right PPC serves early visuomotor transformations and is, therefore, related to direct route priming.     

Dominance of the left oblique view in activating the cortical network for face recognition

Faces in portraits are often depicted from the left 3/4 view (an oblique view of the face that is intermediate between the frontal view and left profile). Here, we used functional magnetic resonance imaging (fMRI) to show that, compared with photographs of right 3/4 views of familiar faces, photographs of left 3/4 views of the same faces elicited stronger neural responses in the right middle occipital/inferior parietal cortex, and right inferior frontal gyrus; which are known to be involved in face recognition. By contrast, there was no differential activation in the temporal cortex including the superior temporal sulcus and fusiform gyrus, which are thought to process face-related visual stimuli at a stage that precedes recognition. We suggest that the preference for the left 3/4 view of faces was produced at a later stage of facial information processing that involves attention or memory retrieval.     

Functional magnetic resonance imaging evidence for binocular interactions in human visual cortex

Using functional magnetic resonance imaging (fMRI), we explored the binocular interactions occurring when subjects viewed dichoptically presented checkerboard stimuli. A flickering radial checkerboard was presented to each eye of the subject, while T2*-weighted images were acquired over the visual cortex with gradient-echo, echoplanar sequences. We compared responses in striate and extrastriate visual cortex under four conditions: both eyes were stimulated at the same time (binocular condition), each eye was stimulated in alternation (monocular condition) or first the one eye then the other eye was stimulated (left eye first - right eye trailing, or vice versa). The results indicate that only the striate area, in and near the calcarine fissure, shows significant differences for these stimulation conditions. These differences are not evident in more remote extrastriate or associational visual areas, although the BOLD response in the stimulation-rest comparison was robust. These results suggest that the effect could be related to inhibitory interactions across ocular dominance columns in striate visual cortex.     

Comparison of effects of pentobarbital and ethanol on the neuronal activity in the posterior parietal association cortex

The problem of this study was whether the effects produced by alcohol in the posterior parietal association cortex are specific to this drug or shared by other centrally acting depressant drugs such as barbiturates. The effect of graded doses of pentobarbital on multineuronal impulse activity was recorded with transdural microelectrode technique in 30 expts. in Brodmann's area 7 of five stump-tailed monkeys (Macaca speciosa). The results were compared with those from 32 expts. performed with alcohol and published separately. The dosage of the two drugs was determined on the basis of the monkeys' sensori-motor coordination which was assessed with a rating scale of reaching accuracy for food rewards. There were several recording sites where the actions of the two drugs were similar at similar behavioural levels of intoxication. However, in the distribution of effects among various functional types of recording sites a significant difference was found between pentobarbital and alcohol. Alcohol commonly diminished cellular activity related to motor behaviour (reaching, grasping) and only rarely responses to somesthetic stimuli, whereas the effects of pentobarbital were the opposite being most common on somatosensory responses and least common on activity related to motor behaviour. Also responses to visual stimuli were more sensitive to pentobarbital than to alcohol. The actions of pentobarbital and alcohol on responses evoked by sensory stimulation differed significantly (P < 0.01). We conclude that significant differences exist in the mechanisms of action of alcohol and barbiturate on the associative systems of the brain.     

Activity in Posterior Parietal Cortex Following Somatosensory Stimulation in Man: Magnetoencephalographic Study Using Spatio-Temporal Source Analysis

We investigated the activation of posterior parietal cortex (PPC) to somatosensory stimulation in humans to determine its fundamental role as a somatosensory associated area using magnetoencephalography (MEG). We studied somatosensory evoked magnetic fields (SEF) after stimulation of median nerve, posterior tibial nerve and lip, and analyzed them by the single dipole model and also by the multidipole model using brain electric source analysis (BESA) system. In single source model analysis, the dipole at the peak latency of short-latency components following each site stimulation were located in the corresponding receptive fields in the primary somatosensory cortex (SI) contralateral to the stimulation. The dipole at the peak latency of the middle latency components were located in bilateral upper bank of Sylvian fissure (SII). By contrast, in the five-dipole model of BESA, the equivalent current dipoles (ECDs) of the middle-latency SEF after stimulation of median nerve and posterior tibial nerve were identified in the contralateral SI and in the bilateral SII and PPC, while all activities of middle-latency SEF after lip stimulation appeared to be restricted in the contralateral SI and bilateral SII. Around 80 msec in latency, the ECD location in PPC after median nerve stimulation was, on the average, 2.4 cm posterior, 2.9 cm medial and 2.6 cm superior to the hand area in SI. The ECD in PPC after posterior tibial nerve stimulation was also located posterior to the foot area in SI, but it was close to the SI area of foot, their distance being approximately 1.3 cm. ECD in PPC was almost equally demonstrated in each hemisphere. These findings suggested that the somatosensory associated cortex in PPC represented somatotopic organization in parallel with homunculus in SI, but the hand area was much wider than the foot area. It was not clear whether the lip area in PPC was absent or was too close to be separated from the SI.     

Donepezil Improves Episodic Memory in Young Individuals Vulnerable to the Effects of Sleep Deprivation

Study Objectives:

We investigated if donepezil, a long-acting orally administered cholinesterase inhibitor, would reduce episodic memory deficits associated with 24 h of sleep deprivation.

Design:

Double-blind, placebo-controlled, crossover study involving 7 laboratory visits over 2 months. Participants underwent 4 functional MRI scans; 2 sessions (donepezil or placebo) followed a normal night''s sleep, and 2 sessions followed a night of sleep deprivation.

Setting:

The study took place in a research laboratory.

Participants:

26 young, healthy volunteers with no history of any sleep, psychiatric, or neurologic disorders.

Interventions:

5 mg of donepezil was taken once daily for approximately 17 days.

Measurements and Results:

Subjects were scanned while performing a semantic judgment task and tested for word recognition outside the scanner 45 minutes later. Sleep deprivation increased the frequency of non-responses at encoding and impaired delayed recognition. No benefit of donepezil was evident when participants were well rested. When sleep deprived, individuals who showed greater performance decline improved with donepezil, whereas more resistant individuals did not benefit. Accompanying these behavioral effects, there was corresponding modulation of task-related activation in functionally relevant brain regions. Brain regions identified in relation to donepezil-induced alteration in non-response rates could be distinguished from regions relating to improved recognition memory. This suggests that donepezil can improve delayed recognition in sleep-deprived persons by improving attention as well as enhancing memory encoding.

Conclusions:

Donepezil reduced decline in recognition performance in individuals vulnerable to the effects of sleep deprivation. Additionally, our findings demonstrate the utility of combined fMRI–behavior evaluation in psychopharmacological studies.

Citation:

Chuah LYM; Chong DL; Chen AK; Rekshan WR; Tan JC; Zheng H; Chee MWL. Donepezil improves episodic memory in young individuals vulnerable to the effects of sleep deprivation. SLEEP 2009;32(8):999-1010.     

Posterior parietal cortex: functional properties of neurons in area 5 during an instructed-delay reaching task within different parts of space

The activity of single neurons was recorded in area 5 while monkeys made parallel arm movements within different parts of space in an instructed-delay reaching task. In this task: (1) extrinsic variables, such as the direction of movement, were dissociated from intrinsic ones, such as the joint configuration used to perform the movements; and (2) the early neural events related to the presentation of the visual stimulus concerning movement direction were dissociated in time from the later events linked to the execution of movement. Under these experimental conditions, cell activity in area 5 changed so that the population of preferred direction vectors of parietal neurons rotated in space in a way which predicted the rotation of the arm necessary to perform the task. This rotation occurred both during the instructed-delay time, when the monkey waited for the go-signal, and during the time interval surrounding the onset of movement. This suggests that reaching to visual targets in area 5 is coded by a mechanism combining somatic and visually derived information within a shoulder- or body-centered coordinate system and that instructed-delay time activity in area 5 reflects not only the composition of the direction signal for reaching but also the spatial configuration of the arm.