Callosal connections of dorsal versus ventral premotor areas in the macaque monkey: a multiple retrograde tracing study

BACKGROUND: The lateral premotor cortex plays a crucial role in visually guided limb movements. It is divided into two main regions, the dorsal (PMd) and ventral (PMv) areas, which are in turn subdivided into functionally and anatomically distinct rostral (PMd-r and PMv-r) and caudal (PMd-c and PMv-c) sub-regions. We analyzed the callosal inputs to these premotor subdivisions following 23 injections of retrograde tracers in eight macaque monkeys. In each monkey, 2–4 distinct tracers were injected in different areas allowing direct comparisons of callosal connectivity in the same brain. RESULTS: Based on large injections covering the entire extent of the corresponding PM area, we found that each area is strongly connected with its counterpart in the opposite hemisphere. Callosal connectivity with the other premotor areas, the primary motor cortex, prefrontal cortex and somatosensory cortex varied from one area to another. The most extensive callosal inputs terminate in PMd-r and PMd-c, with PMd-r strongly connected with prefrontal cortex. Callosal inputs to PMv-c are more extensive than those to PMv-r, whose connections are restricted to its counterpart area. Quantitative analysis of labelled cells confirms these general findings, and allows an assessment of the relative strength of callosal inputs. CONCLUSION: PMd-r and PMv-r receive their strongest callosal inputs from their respective counterpart areas, whereas PMd-c and PMv-c receive strong inputs from heterotopic areas as well (namely from PMd-r and PMv-r, respectively). Finally, PMd-r stands out as the lateral premotor area with the strongest inputs from the prefrontal cortex, and only the PMd-c and PMv-c receive weak callosal inputs from M1

Reaching activity in parietal area V6A of macaque: eye influence on arm activity or retinocentric coding of reaching movements?

Parietal area V6A contains neurons modulated by the direction of gaze as well as neurons able to code the direction of arm movement. The present study was aimed to disentangle the gaze effect from the effect of reaching activity upon single V6A neurons. To this purpose, we used a visuomotor task in which the direction of arm movement remained constant while the animal changed the direction of gaze. Gaze direction modulated reach-related activity in about two-thirds of tested neurons. In several cases, modulations were not due to the eye-position signal per se, the apparent eye-position modulation being just an epiphenomenon. The real modulating factor was the location of reaching target with respect to the point gazed by the animal, that is, the retinotopic coordinates towards which the action of reaching occurred. Comparison of neural discharge of the same cell during execution of foveated and non-foveated reaching movements, performed towards the same or different spatial locations, confirmed that in a part of V6A neurons reaching activity is coded retinocentrically. In other neurons, reaching activity is coded spatially, depending on the direction of reaching movement regardless of where the animal was looking at. The majority of V6A reaching neurons use a system that encompasses both of these reference frames. These results are in line with the view of a progressive visuomotor transformation in the dorsal visual stream, that changes the frame of reference from the retinocentric one, typically used by the visual system, to the arm-centred one, typically used by the motor system

Involvement of the subthalamic nucleus in engagement with behaviourally relevant stimuli

In this study we investigate how the basal ganglia (BG) may process the behavioural relevance of environmental cues by recording local field potentials (LFPs) in the subthalamic nucleus of patients with Parkinson’s disease who had undergone implantation of electrodes for deep brain stimulation. Fourteen patients were recorded as they performed a paradigm dissociating warning cue presentation from programming related to execution of specific tasks. Target and non-target warning cues of differing behavioural relevance were contrasted, and we evaluated if warning cue-evoked activities varied according to whether the eventual task to be performed was motor or cognitive and whether patients were receiving or withdrawn from dopaminergic therapy. Warning cues evoked a complex temporal sequence of activities with three epochs over the 760 ms following the onset of the warning cue. In contrast to the initial evoked LFP, evoked activities over two later periods were significantly influenced by behavioural relevance and by treatment state. The early activity was likely related to the initial orientating of attention induced by a novel target, while the delayed responses in our paradigm may reflect processing related to the non-motor resource implications of cues. The results suggest that the BG are intimately involved in the evaluation of changes in the environment and of their behavioural significance. The latter process is partly modulated by dopamine. Weakness in this function might contribute to the behavioural impairment that can follow BG lesions and surgery

Dopamine Innervation in the Thalamus: Monkey versus Rat

We recently identified the thalamic dopaminergic system in the human and macaque monkey brains, and, based on earlier reports on the paucity of dopamine in the rat thalamus, hypothesized that this dopaminergic system was particularly developed in primates. Here we test this hypothesis using immunohistochemistry against the dopamine transporter (DAT) in adult macaque and rat brains. The extent and density of DAT-immunoreactive (-ir) axons were remarkably greater in the macaque dorsal thalamus, where the mediodorsal association nucleus and the ventral motor nuclei held the densest immunolabeling. In contrast, sparse DAT immunolabeling was present in the rat dorsal thalamus; it was mainly located in the mediodorsal, paraventricular, ventral medial, and ventral lateral nuclei. The reticular nucleus, zona incerta, and lateral habenular nucleus held numerous DAT-ir axons in both species. Ultrastructural analysis in the macaque mediodorsal nucleus revealed that thalamic interneurons are a main postsynaptic target of DAT-ir axons; this suggests that the marked expansion of the dopamine innervation in the primate in comparison to the rodent thalamus may be related to the presence of a sizable interneuron population in primates. We remark that it is important to be aware of brain species differences when using animal models of human brain disease

Visual Motion Responses in the Posterior Cingulate Sulcus: A Comparison to V5/MT and MST

Motion processing regions apart from V5+/MT+ are still relatively poorly understood. Here, we used functional magnetic resonance imaging to perform a detailed functional analysis of the recently described cingulate sulcus visual area (CSv) in the dorsal posterior cingulate cortex. We used distinct types of visual motion stimuli to compare CSv with V5/MT and MST, including a visual pursuit paradigm. Both V5/MT and MST preferred 3D flow over 2D planar motion, responded less yet substantially to random motion, had a strong preference for contralateral versus ipsilateral stimulation, and responded nearly equally to contralateral and to full-field stimuli. In contrast, CSv had a pronounced preference to 2D planar motion over 3D flow, did not respond to random motion, had a weak and nonsignificant lateralization that was significantly smaller than that of MST, and strongly preferred full-field over contralateral stimuli. In addition, CSv had a better capability to integrate eye movements with retinal motion compared with V5/MT and MST. CSv thus differs from V5+/MT+ by its unique preference to full-field, coherent, and planar motion cues. These results place CSv in a good position to process visual cues related to self-induced motion, in particular those associated to eye or lateral head movements

Cortical Connections to Area TE in Monkey: Hybrid Modular and Distributed Organization

To investigate the fine anatomical organization of cortical inputs to visual association area TE, 2–3 small injections of retrograde tracers were made in macaque monkeys. Injections were made as a terminal procedure, after optical imaging and electrophysiological recording, and targeted to patches physiologically identified as object-selective. Retrogradely labeled neurons occurred in several unimodal visual areas, the superior temporal sulcus, intraparietal sulcus (IPS), and prefrontal cortex (PFC), consistent with previous studies. Despite the small injection size (<0.5 mm wide), the projection foci in visual areas, but not in IPS or PFC, were spatially widespread (4–6 mm in extent), and predominantly consisted of neurons labeled by only one of the injections. This can be seen as a quasi-modular organization. In addition, within each projection focus, there were scattered neurons projecting to one of the other injections, together with some double-labeled (DL) neurons, in a more distributed pattern. Finally, projection foci included smaller “hotspots,” consisting of intermixed neurons, single-labeled by the different injections, and DL neurons. DL neurons are likely the result of axons having extended, spatially separated terminal arbors, as demonstrated by anterograde experiments. These results suggest a complex, hybrid connectivity architecture, with both modular and distributed components

Trigeminal ganglion innervates the auditory brainstem

A neural connection between the trigeminal ganglion and the auditory brainstem was investigated by using retrograde and anterograde tract tracing methods: iontophoretic injections of biocytin or biotinylated dextran-amine (BDA) were made into the guinea pig trigeminal ganglion, and anterograde labeling was examined in the cochlear nucleus and superior olivary complex. Terminal labeling after biocytin and BDA injections into the ganglion was found to be most dense in the marginal cell area and secondarily in the magnocellular area of the ventral cochlear nucleus (VCN). Anterograde and retrograde labeling was also seen in the shell regions of the lateral superior olivary complex and in periolivary regions. The labeling was seen in the neuropil, on neuronal somata, and in regions surrounding blood vessels. Retrograde labeling was investigated using either wheatgerm agglutinin-horseradish peroxidase (WGA-HRP), BDA, or a fluorescent tracer, iontophoretically injected into the VCN. Cells filled by retrograde labeling were found in the ophthalmic and mandibular divisions of the trigeminal ganglion. We have previously shown that these divisions project to the cochlea and middle ear, respectively. This study provides the first evidence that the trigeminal ganglion innervates the cochlear nucleus and superior olivary complex. This projection from a predominantly somatosensory ganglion may be related to integration mechanisms involving the auditory end organ and its central targets. J. Comp. Neurol. 419:271–285, 2000. © 2000 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34459/1/1_ftp.pd

Weight Consistency Specifies Regularities of Macaque Cortical Networks

To what extent cortical pathways show significant weight differences and whether these differences are consistent across animals (thereby comprising robust connectivity profiles) is an important and unresolved neuroanatomical issue. Here we report a quantitative retrograde tracer analysis in the cynomolgus macaque monkey of the weight consistency of the afferents of cortical areas across brains via calculation of a weight index (fraction of labeled neurons, FLN). Injection in 8 cortical areas (3 occipital plus 5 in the other lobes) revealed a consistent pattern: small subcortical input (1.3% cumulative FLN), high local intrinsic connectivity (80% FLN), high-input form neighboring areas (15% cumulative FLN), and weak long-range corticocortical connectivity (3% cumulative FLN). Corticocortical FLN values of projections to areas V1, V2, and V4 showed heavy-tailed, lognormal distributions spanning 5 orders of magnitude that were consistent, demonstrating significant connectivity profiles. These results indicate that 1) connection weight heterogeneity plays an important role in determining cortical network specificity, 2) high investment in local projections highlights the importance of local processing, and 3) transmission of information across multiple hierarchy levels mainly involves pathways having low FLN values

Brain Effective Connectivity During Motor-Imagery and Execution Following Stroke and Rehabilitation

Brain areas within the motor system interact directly or indirectly during motor-imagery and motor-execution tasks. These interactions and their functionality can change following stroke and recovery. How brain network interactions reorganize and recover their functionality during recovery and treatment following stroke are not well understood. To contribute to answering these questions, we recorded blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) signals from10 stroke survivors and evaluated dynamical causal modeling (DCM)-based effective connectivity among three motor areas: primary motor cortex (M1), premotor cortex (PMC) and supplementary motor area (SMA), during motor-imagery and motor-execution tasks. We compared the connectivity between affected and unaffected hemispheres before and after mental practice and combined mental practice and physical therapy as treatments. The treatment (intervention) period varied in length between 14 to 51 days but all patients received the same dose of 60 h of treatment. Using Bayesian model selection (BMS) approach in the DCMapproach, wefound that, after intervention, the same network dominated during motor-imagery and motor-execution tasks butmodulatory parameters suggested a suppressive influence of SM A on M1 during the motor-imagery task whereas the influence of SM A on M1 was unrestricted during themotor-execution task.We found that the intervention caused a reorganization of the network during both tasks for unaffected as well as for the affected hemisphere. Using Bayesian model averaging (BMA) approach, we found that the intervention improved the regional connectivity among the motor areas during both the tasks. The connectivity between PMCandM1was stronger inmotor-imagery taskswhereas the connectivity from PMC to M1, SM A to M1 dominated in motor-execution tasks. There was significant behavioral improvement (p = 0.001) in sensation and motor movements because of the intervention as reflected by behavioral Fugl-Meyer (FMA)measures,whichwere significantly correlated (p=0.05)with a subset of connectivity. These findings suggest that PMC andM1 play a crucial role duringmotor-imagery aswell as during motorexecution task. In addition,M1 causesmore exchange of causal information amongmotor areas during a motorexecution task than during a motor-imagery task due to its interaction with SM A. This study expands our understanding of motor network involved during two different tasks, which are commonly used during rehabilitation following stroke. A clear understanding of the effective connectivity networks leads to a better treatment in helping stroke survivors regain motor ability