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Functional structuration of the cerebellar efferent network involved in forelimb control, during processing of an associative conditioning.

A simplified sensorimotor pathway was subjected to an associative conditioning in fully awake cats. It was defined by the location of electrodes for applying the conditional stimulation (CS) in the cerebellar interpositus nucleus (IN) and the unconditional stimulation (UCS) on the skin of the forelimb. Electrodes chronically implanted all along the pathway allowed the simultaneous study of the motor and the neurobiological effects of conditioning. Persistent motor changes were observed in parallel with interposito-rubral and thalamocortical synaptic efficiency changes. The two kinds of event evolved similarly and significant correlations were found between them. Changes appeared to be induced according to modalities similar to those underlying elementary mechanisms of neuronal plasticity. The modulations of thalamocortical synaptic efficiency inside the primary motor cortex (MI) determined a new pattern of distribution of cerebellar effects on musculature, indicating that in adult brains the functional organization of central motor pathways is not definitely rigid it can still be subject to adaptive modifications.

Animals↗

Role of neuroimaging in the management of seizure disorders.

Neuroimaging is one of the most important advances made in the past decade in the management of seizure disorders. Magnetic resonance imaging (MRI) has increased substantially the ability to detect causes of seizure disorders, to plan medical or surgical therapy, and to prognosticate the outcome of disorders and therapy. However, MRI must be performed with techniques that will maximize the detection of potentially epileptogenic lesions, especially in candidates for epilepsy surgery. Functional imaging has an established role in evaluating patients for epilepsy surgery. It is relied on when results from standard diagnostic methods, such as clinical information, electroencephalography, and MRI, are insufficient to localize the seizure focus. Also, functional imaging is a reportedly reliable alternative to invasive methods for identifying language, memory, and sensorimotor areas of the cerebral cortex. Despite the availability of multimodality imaging, the epileptogenic zone is not determined solely by a single imaging modality. Evidence and experience have shown that concordance of results from clinical, electrophysiologic, and neuroimaging studies is needed to identify the epileptogenic zone accurately. With modern techniques in image processing, multimodality imaging can integrate the location of abnormal electroencephalographic, structural, and functional imaging foci on a "map" of the patient's brain. Computer image-guided surgery allows surgically exact implantation of intracranial electrodes and resection of abnormal structural or functional imaging foci. These techniques decrease the risk of morbidity associated with epilepsy surgery and enhance the probability of postsurgical seizure control.

Adolescent↗

BOLD coherence reveals segregated functional neural interactions when adapting to distinct torque perturbations.

In the natural world, we experience and adapt to multiple extrinsic perturbations. This poses a challenge to neural circuits in discriminating between different context-appropriate responses. Using event-related fMRI, we characterized the neural dynamics involved in this process by randomly delivering a position- or velocity-dependent torque perturbation to subjects' arms during a target-capture task. Each perturbation was color-cued during movement preparation to provide contextual information. Although trajectories differed between perturbations, subjects significantly reduced error under both conditions. This was paralleled by reduced BOLD signal in the right dentate nucleus, the left sensorimotor cortex, and the left intraparietal sulcus. Trials included "NoGo" conditions to dissociate activity related to preparation from execution and adaptation. Subsequent analysis identified perturbation-specific neural processes underlying preparation ("NoGo") and adaptation ("Go") early and late into learning. Between-perturbation comparisons of BOLD magnitude revealed negligible differences for both preparation and adaptation trials. However, a network-level analysis of BOLD coherence revealed that by late learning, response preparation ("NoGo") was attributed to a relative focusing of coherence within cortical and basal ganglia networks in both perturbation conditions, demonstrating a common network interaction for establishing arbitrary visuomotor associations. Conversely, late-learning adaptation ("Go") was attributed to a focusing of BOLD coherence between a cortical-basal ganglia network in the viscous condition and between a cortical-cerebellar network in the positional condition. Our findings demonstrate that trial-to-trial acquisition of two distinct adaptive responses is attributed not to anatomically segregated regions, but to differential functional interactions within common sensorimotor circuits.

Adaptation, Physiological↗

[Stomatognathic system and body posture in children with sensoriomotor deficits].

BACKGROUND: Literature points that body posture is an important aspect in the treatment of children with sensorimotor deficits. Considering individuals with cerebral palsy, reflexes are often more intense than reactions of rectification and equilibrium, causing, therefore, a delay or obstacle in cervical, torso and hip control. This delay has as a consequence an impact on the Stomatognathic System. AIM: To verify the relation between body posture and the Stomatognathic System in this population, regarding posture and function, and its effectiveness in the process of speech-language intervention. METHOD: 17 children with sensorimotor deficits, aged between 1 and 6:3 years, were submitted to an initial assessment, followed by speech-language intervention and re-assessment. Speech-language intervention occurred for a period of 10 months, with weekly individual sessions, always in the presence of the caretaker. All sessions were transcribed in a specific protocol and the assessment and re-assessment sessions were videotaped. RESULTS: A statistically significant improvement of stomatognathic system in 100% of the children was observed, not only of the isolated structures, but also of the whole system. The same was observed for the assessed functions. CONCLUSION: The improvement of body posture of the studied children favored significantly the development and improvement of the stomatognathic system regarding the aspects of posture and function.

Cheek↗

Intranigral transplants of GABA-rich striatal tissue induce behavioral recovery in the rat Parkinson model and promote the effects obtained by intrastriatal dopaminergic transplants.

Intrastriatal transplantation of fetal ventral mesencephalon (VM) is currently explored as a potential clinical therapy in Parkinson's disease (PD). Although providing substantial benefit for the patient, behavioral recovery so far obtained with intrastriatal VM grafts is not complete. Using the 6-hydroxydopamine lesion model of PD, we show here that near-complete restoration of the striatal dopamine (DA) innervation can be achieved by multiple intrastriatal microtransplants of fetal DA cells; nevertheless, complete recovery in complex sensorimotor behaviors was not obtained in these animals. In line with the current model of basal ganglia function, this suggests that the lesion-induced overactivity of the basal ganglia output structures, i.e., the substantia nigra (SN) and the entopeduncular nucleus, may not be completely reversed by intrastriatal VM grafts. In the present study, we have transplanted fetal VM tissue or fetal striatal tissue, as a source of DA and GABA neurons, respectively, into the SN of DA-depleted rats. Intranigral VM grafts induced behavioral recovery in some sensorimotor behaviors (forelimb akinesia and balance tests), but the effect did not exceed the recovery observed after intrastriatal VM grafts. Intranigral grafts of striatal tissue induced a pattern of functional recovery which was distinctly different from that observed after intranigral VM grafts, and recovery in coordinated forelimb use in the paw-reaching test was even more pronounced than after intrastriatal transplantation of VM cells. Combined transplantation of DA neurons into the striatum and GABA-rich striatal neurons into the SN induced additive effects of behavioral recovery observed in the forelimb akinesia test. We propose that intranigral striatal transplants, by a GABA-mediated inhibitory action, can reduce the overactivity of the host SN projection neurons and can induce significant recovery in complex motor behavior in the rat PD model and that such grafts may be used to increase the overall functional efficacy of intrastriatal VM grafts.

Animals↗

Organization of cortical and subcortical projections to the feline insular visual area, IVA.

Extracellular recordings with carbon fiber-filled microelectrodes were used to identify the visually responsive area within the insular cortex (referred to hereafter as the insular visual area, IVA) of anaesthetized cats. Broadly speaking, IVA comprises the cortex surrounding the anterior ectosylvian sulcus (AEs) along its ventral bank and the major portion of the anterior sylvian gyrus. Visually sensitive cells were recorded along the whole length of the AEs. In the same animals, the afferent connections of IVA were studied through the use of the retrograde tracers wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) and fluorescent Diamidino yellow (DY), in combination with standard electrophysiological stimulation and recording techniques. The results indicate that: (1) the IVA receives a wide variety of telencephalic inputs, not only from visual, sensorimotor, auditory, limbic and association cortical areas, and from the claustrum, amygdala and basal nucleus of Meynert, as well, but also from the diencephalic projections arising mainly from the lateralis medialis-suprage niculate nuclear complex (LM-Sg) and the ventral medial nucleus (VM). (2) The gyral part of IVA (gIVA) receives afferents mainly from the lateral part of the lateral suprasylvian visual area (LS) throughout almost its entire length, as well as from area 20, the posterior suprasylvian sulcal area (PS), the frontal eye fields, areas 6 and 36, and almost the whole length of the cortical area lying along the anterior ectosylvian sulcus (AEs). (3) By contrast with (2), the sulcal part of IVA (sIVA) which corresponds to the anterior part of the anterior ectosylvian visual area (AEV) of Norita et al. ('86), receives cortical projections mainly from the lateral and medial parts of the anterior half of LS, area 20, PS, the frontal eye fields, area 36, and most parts of the cortical area extending along the AEs. (4) Subcortically, IVA receives thalamic afferents mainly from VM and LM-Sg. The connections between IVA and LM-Sg are organized topographically, with the more anterior part of IVA being related to the more ventral portion of LM-Sg, and with sIVA being related chiefly to the mid-portions of LM-Sg. These results thus suggest that IVA may function as an integrative centre among structures belonging to the extrageniculostriate system, the sensorimotor system, as well as to the limbic system. Furthermore, our electrophysiological and anatomical findings, together with previous reports concerning AEV, suggest that the posterior part of AEV (AEV proper) is distinctive from gIVA, and that the sIVA apparently serves as a transitional region between AEV and gIVA.

Afferent Pathways↗

Role of the pedunculopontine tegmental nucleus in sensorimotor gating and reward-related behavior in rats.

RATIONALE: The pedunculopontine tegmental nucleus (PPTg) is involved in the execution and regulation of a variety of behaviors. Most investigations used brain lesions that have certain disadvantages, such as functional compensation over time. OBJECTIVES: In the present study, we investigated by temporary, reversible inhibition of neurons the role of the PPTg in sensorimotor gating, measured as prepulse inhibition (PPI) of the acoustic startle response (ASR) using variable interstimulus intervals (ISI). In a second set of experiments we examined by the same technique the role of the PPTg in a progressive-ratio instrumental response task. METHODS: Local infusions of the GABA(A)-receptor agonist muscimol (0.05 microg and 0.5 microg/0.3 microl, or vehicle) were applied through indwelling microinfusion cannulae into the PPTg of freely moving rats. ASR and PPI were measured using acoustic stimuli of 100 dB (pulse) and 80 dB (prepulse) using ISIs of 25, 120, 520 and 1,020 ms. Instrumental behavior (lever pressing for casein pellets) was assessed in a Skinner box. Motor activity was measured in an open field. RESULTS: Intra-PPTg infusions of muscimol dose-dependently attenuated PPI at ISIs of 120 ms and 520 ms, but not at longer or shorter ISIs. ASR magnitude in pulse-alone trials was not significantly affected. Intra-PPTg infusion of 0.5 microg muscimol reduced the break point of instrumental responding (testing sequence where the rats fail to respond according to an increased ratio of reinforcement). No effects on food-preference and open-field activity were found. CONCLUSIONS: These findings suggest that GABAergic neurotransmission in the PPTg plays an important role for sensorimotor gating at intermediate ISIs and for response selection under demanding schedules of reinforcement.

Acetylcholinesterase↗

Functional significance of the ipsilateral hemisphere during movement of the affected hand after stroke.

Previous fMRI observations have suggested increased task-related activation of the ipsilateral cerebral motor cortex in patients recovering from stroke. This is generally taken to infer an increased output from this area, although the functional relevance of this has been questioned. Here, we use directed EEG coherence to reveal whether there is increased informational flow from the ipsilateral motor cortex following motor stroke, and through correlation with degree of recovery, establish that this pattern of activity is associated with limited functional improvement. Unrecovered (n = 14), recovered (n = 11) patients and healthy subjects (n = 16) performed an isometric grip task with either hand that corresponded to 25% of individual maximum force, while EEG was recorded. For unrecovered stroke patients, most task-related information flow between the sensorimotor cortices in the low beta band of the EEG came from the ipsilateral (undamaged) hemisphere during grip with the affected hand. This was not the case when they gripped with their unaffected hand, when cortical activity was driven from the contralateral sensorimotor cortex. The latter pattern was also seen in recovered patients and controls. These findings suggest a functional role for the ipsilateral hemisphere in organizing movement of the impaired limb following stroke, but only in those patients that do not make a good functional recovery. Patients making a fuller recovery organize movement-related cortical activity from the hemisphere contralateral to movement.

Adolescent↗

Structure of dependent relationships between neurons in the sensorimotor cortex of the left and right hemispheres in rabbits in immobilization catatonia.

Dependence in the activity of sensorimotor cortex neurons recorded simultaneously in the left and right hemispheres was detected in rabbits in baseline conditions, during the state of immobilization ("animal hypnosis"), and recovery of animals from this state. In baseline conditions, the total percentage of dependent relationships between close-lying (within 50 microm) neurons in the left hemisphere was significantly smaller than in the right hemisphere and did not change either in the state of immobilization or on recovery from it. The total percentage of dependent relationships between close-lying neurons in the right hemisphere decreased significantly during immobilization and returned to baseline levels on recovery from this state. The percentage of dependent relationships between distant (500 microm) neurons in immobilization, conversely, showed no change in the cortex of the right hemisphere, though it changed significantly in the cortex of the left hemisphere, returning to baseline values when the rabbits recovered from this state. Further analysis showed that this cortical interhemisphere asymmetry was based on the asymmetrical activity of individual neurons and small neuronal populations. Thus, changes in the structure of dependent relationships between neurons in microareas of the cortex of the left and macroareas of the cortex of the right hemisphere could be in different directions, while changes in microareas of the right hemisphere and macroareas of the left hemisphere were synergistic. Thus, asymmetry was detected at different levels of neuronal combinations (neuron pairs, micro- and macrogroups of neurons), which suggests mosaicism in neuron structure, which ultimately leads to overall functional asymmetry in "animal hypnosis." Some changes in the structure of dependent relationships between sensorimotor cortex neurons arising in "animal hypnosis" persisted or even became more marked after recovery of animals from this state.

Action Potentials↗

[Function of the superior colliculi of the corpora quadrigemina during creation of a local focus of increased excitability in the mesencephalic reticular formation and sensomotor cortex].

In chronic experiments on waking rabbits, the foci of heightened excitability in the sensorimotor cortex and mesencephalic reticular formation affected in a similar way the background neuronal activity in the superior colliculi and that evoked by light stimuli. The effect was manifested in elimination of inhibitory pauses in the neuronal response to light stimulus and in a general increase of discharge frequency. Similarity of the cortical and reticular influences is due to their possible mediation by the same collicular interneurones participating in inhibitory pauses formation in the process of backward inhibition. Increased neuronal activity in the superior colliculi under the action of local foci in the sensorimotor cortex and mesencephalic reticular formation correlated with appearance of forelimb motor reaction to isolated light stimulus testifying to a formation of a functional connection between the visual and motor analyzers. Possible role of the superior colliculi in this process and their participation in the formation of a visually controlled reaction is discussed.

Animals↗

[Functional neural reorganization following ischemic stroke in the precentral knob: an fMRI study].

We evaluated a 63 year-old, right-handed woman by functional MRI (fMRI) in the early and the recovery stages following a cerebral infarction in the right precentral knob. An activated signal in the ipsilateral sensorimotor cortex and contralateral supplementary motor cortex during deteriorated hand grasping (left) was observed in the early stages, whereas being unable to detect in the functionally recovered period. When simultaneous bilateral hand grasping was performed, the activated signal around infarct region was enlarged in recovered period. The functionally neural reorganization processes relating recovered hand movement after localized cortical infarction (precentral knob) was suggested.

Cerebral Infarction↗

The role of the inferior collicular cortex in the neonatal rat: sensorimotor modulation.

A tail pinch in rats up to 10 days of age produces a spectrum of motor behaviors characterized by forelimb paddling, hindlimb treading and occasional curling and rolling of the torso, a behavioral pattern similar to the seizure behaviors electrically-elicited from the inferior collicular cortex of 5- or 10-day-old rats. In 5-day-old rats, these tail pinch-induced paddling and treading behaviors coincided with afterdischarge-like EEG activity recorded from the seizure-sensitive site in the inferior collicular cortex. In contrast, no change in the EEG activity occurred in an adjacent seizure-insensitive site during these tail pinch-induced behaviors. Similar electrographic-behavioral synchrony was found in 10-day-old rats, but by 16 days of age, as in the adult rat, a tail pinch stimulus did not induce post-stimulus behavioral changes or afterdischarge-like EEG activity. Since auditory function does not develop until 12-14 days of age in the rat, we propose that the inferior collicular cortex modulates sensorimotor integration in the neonatal rat, prior to assumption of this function by the cerebral cortex.

Animals↗

Anorectal sensorimotor dysfunction in fecal incontinence and diabetes mellitus. Modification with biofeedback therapy.

We studied anorectal sensory and motor function in 14 diabetics with fecal incontinence and compared the results with those in 13 continent diabetics, 31 nondiabetics with fecal incontinence, and 11 continent nondiabetics. The threshold volume at which diabetic patients with fecal incontinence experienced rectal sensation was higher (25.0 +/- 3.4 ml [mean +/- S.E.M.]) than that in continent diabetics (13.0 +/- 2.4 ml) or nondiabetics with or without incontinence (14.5 +/- 1.5 and 12.5 +/- 1.8 ml, respectively; P less than 0.02). Biofeedback conditioning in 11 incontinent diabetics led to normal sensory thresholds in six of seven patients with pretreatment thresholds above 20 ml; five of these six became continent. Biofeedback also improved external-sphincter function in nine diabetics, eight of whom became continent. Overall, 8 of 11 diabetics had a reduction in fecal soiling after biofeedback therapy. We conclude that fecal incontinence in diabetics may be caused by decreased rectal sensation or impaired function of the external sphincter or both, and that these abnormalities can often be improved by biofeedback therapy with resultant reestablishment of bowel control.

Adult↗

Sensorimotor and cognitive deficits after transient middle cerebral artery occlusion in the mouse.

Whereas behavioral impairments after stroke are increasingly studied in the rat, little is known about the long-term functional consequences of focal ischemia in the mouse. To address this issue, Swiss mice underwent transient (60 min) intraluminal occlusion of the middle cerebral artery (MCAo) or sham surgery. Sensorimotor (chimney, accelerating rotarod, pole, corner, adhesive removal and staircase tests) and cognitive (passive avoidance and Morris water maze) performances were regularly assessed during 1 month, after which the final histological lesion was measured. Motor coordination and balance, assessed by the chimney and rotarod tests, were transiently altered by MCAo. Moreover, bradykinesia was evidenced by the pole test. The most striking and long-lasting (1 month) sensorimotor deficits were postural asymmetries on the corner test, bilateral skilled forepaw reaching deficits on the staircase test and a contralateral sensorimotor impairment on the adhesive removal test. MCAo animals showed normal spatial learning abilities on the Morris water maze test, but they displayed learning deficits measured by the passive avoidance test. This latter deficit was significantly correlated with both cortical and striatal damage. Our findings demonstrate the usefulness of three tests that had never been reported in the mouse after ischemia: the adhesive removal, staircase and pole tests, which showed deficits 1 month after ischemia and should therefore constitute meaningful tools in mice for assessing both neuroprotective and regenerative therapies in stroke preclinical studies.

Animals↗

Growth factors and stem cells as treatments for stroke recovery.

Both polypeptide growth factors and stem cell populations from bone marrow and umbilical cord blood hold promise as treatments to enhance neurologic recovery after stroke. Growth factors may exert their effects through stimulation of neural sprouting and enhancement of endogenous progenitor cell proliferation, migration, and differentiation in brain. Exogenous stem cells may exert their effects by acting as miniature "factories" for trophic substances in the poststroke brain. The combination of growth factors and stem cells may be more effective than either treatment alone. Stroke recovery represents a new and relatively untested target for stroke therapeutics. Whereas acute stroke treatments focus on agents that dissolve blot clots (thrombolytics) and antagonize cell death (neuroprotective agents), stroke recovery treatments are likely to enhance structural and functional reorganization (plasticity) of the damaged brain. Successful clinical trials of stroke recovery-promoting agents are likely to be quite different from trials testing acute stroke therapies. In particular, the time window of effective treatment to enhance stroke recovery is likely to be far longer than that for acute stroke treatments, perhaps days or weeks rather than minutes or hours after stroke. This longer time window means that time is available for careful screening and testing of potential subjects for stroke recovery trials, both in terms of size and location of cerebral infarcts and in type and severity of neurologic deficits. Detailed baseline information can be obtained for each patient against which eventual clinical outcome can be compared. Finally, separate and detailed outcome measures can be obtained in both the sensorimotor and cognitive neurologic spheres, because it is possible that these two kinds of function may recover differently or be differentially responsive to recovery-promoting treatments. Stroke recovery represents an important and underexplored opportunity for the development of new stroke treatments.

Bone Morphogenetic Protein 7↗

The effect of handedness on cortical motor activation during simple bilateral movements.

The neuronal correlates of handedness are still poorly understood. Here we used event-related functional magnetic resonance imaging to investigate the impact of handedness on neuronal activation of the primary sensorimotor cortex, supplementary motor area and dorsal premotor cortex during simple unilateral and bilateral finger movements. In 16 right-handed and 16 left-handed individuals, we mapped changes in regional neuronal activity while participants responded to four symbolic cues presented in a pseudorandom order. According to pre-specified cues, they pressed a button with their right, left or both index fingers or withheld a response. For unilateral right index finger button presses, reaction times, motor and premotor activity were the same for both right- and left-handers. Compared with right-handers, left-handers had shorter reaction times with unilateral left index finger button presses, along with greater activation of the supplementary motor area and right frontal opercular cortex. Simultaneous bilateral compared with unilateral button presses led to a relative increase of activity in the right and left dorsal premotor cortex and the right primary sensorimotor cortex in right but not left-handers. Neither right nor left-handers showed any tendency during bilateral button presses towards faster responses with the dominant hand and the reaction times were equal in the two groups. Therefore, we conclude that the relative increase of activity in dorsal premotor and right primary sensorimotor cortices in right-handers represents a genuine difference in bimanual motor control related to handedness.

Adult↗

Toxicological Assessment of Melamine-Functionalized Graphene Oxide and Carbon Nanotubes Using Zebrafish Models.

Graphene oxide (GO) and carbon nanotube (CNT)-based nanomaterials have attracted significant interest in various industrial and biomedical applications due to their unique physicochemical properties; however, concerns about their potential toxicity, especially when modified with additives like melamine (M), remain largely unresolved. This study investigates the toxicological effects and underlying mechanisms of graphene oxide-melamine (GO-M) and carbon nanotube-melamine (CNT-M) nanoparticles in zebrafish (Danio rerio) embryos and larvae. To this end, developmental toxicity, phenotypic and behavioral changes, as well as histopathological and immunofluorescence alterations, were evaluated following acute exposure to GO-M and CNT-M nanoparticles at concentrations of 5, 10, and 20 mg/L. Results showed that both nanoparticles delayed larval hatching, particularly at higher concentrations (10 and 20 mg/L). Malformations were observed at 20 mg/L in the GO-M group and at 10 and 20 mg/L in the CNT-M group. Additionally, significant changes in larval length and eye area were observed at all concentrations for both nanoparticles. Behavioral assessments revealed that CNT-M exposure at 10 and 20 mg/L significantly impaired head sensorimotor reflexes, while all concentrations affected tail reflexes. In contrast, GO-M exposure did not significantly alter sensorimotor responses. These findings suggest differential toxic mechanisms and neurobehavioral effects of GO-M and CNT-M nanoparticles during early zebrafish development.

Animals↗

Dopaminergic modulation of cortical function in patients with Parkinson's disease.

Patients with idiopathic Parkinson's disease suffer not only from classic motor symptoms, but from deficits in cognitive function, primarily those subserved by the prefrontal cortex as well. The aim of the current study was to investigate the modulatory effects of dopaminergic therapy on neural systems subserving working memory and motor function in patients with Parkinson's disease. Ten patients with stage I and II Parkinson's disease were studied with functional magnetic resonance imaging, during a relatively hypodopaminergic state (ie, 12 hours after a last dose of dopamimetic treatment), and again during a dopamine-replete state. Functional magnetic resonance imaging was performed under three conditions: a working memory task, a cued sensorimotor task and rest. Consistent with prior data, the cortical motor regions activated during the motor task showed greater activation during the dopamine-replete state; however, the cortical regions subserving working memory displayed greater activation during the hypodopaminergic state. Interestingly, the increase in cortical activation during the working memory task in the hypodopaminergic state positively correlated with errors in task performance, and the increased activation in the cortical motor regions during the dopamine-replete state was positively correlated with improvement in motor function. These results support evidence from basic research that dopamine modulates cortical networks subserving working memory and motor function via two distinct mechanisms: nigrostriatal projections facilitate motor function indirectly via thalamic projections to motor cortices, whereas the mesocortical dopaminergic system facilitates working memory function via direct inputs to prefrontal cortex. The results are also consistent with evidence that the hypodopaminergic state is associated with decreased efficiency of prefrontal cortical information processing and that dopaminergic therapy improves the physiological efficiency of this region.

Brain Chemistry↗