Direct evidence for a binding between cognitive and motor functions in humans: a TMS study

During voluntary motor actions, the cortico-spinal (CS) excitability is known to be modulated, on the one hand by cognitive (intention-related) processes and, on the other hand, by motor (performance-related) processes. Here, we studied the way these processes interact in the tuning of CS excitability during voluntary wrist movement. We used transcranial magnetic stimulation (TMS) both as a reliable tool for quantifying the CS excitability, through the motor-evoked potentials (MEPs), and as a central perturbation evoking a movement (because the stimulation intensity was above threshold) with subjects instructed to prepare (without changing their muscle activation) either to "let go" or to "resist" to this evoked movement. We studied the simultaneous evolution of both the motor performance and the MEPs in the wrist flexor and extensor, separately for the successful trials (on average, 66% of the trials whatever the condition) and the unsuccessful trials; this allowed us to dissociate the intention- and performance-related processes. To their great surprise, subjects were found able to cognitively prepare themselves to resist a TMS-induced central perturbation; they all reported an important cognitive effort on the evoked movement. Moreover, because TMS only evoked short-latency MEPs (and no long-latency components), the amplitude of these short-latency MEPs was found to be related in a continuous way to the actual movement whatever the prior intention. These results demonstrate that prior intention allows an anticipatory modulation of the CS excitability, which is not only selective (as already known) but also efficient, giving the intended motor behavior a real chance to be realized. This constitutes a direct evidence of the role of the CS excitability in the binding between cognitive and motor processes in humans.     

Relations between aging sensory/sensorimotor and cognitive functions

Recent evidence is reviewed to examine relations among sensory, sensorimotor, and cognitive aging. Age-heterogeneous cross-sectional data sets show substantial covariation among sensory, sensorimotor and intellectual abilities, and an increase in covariation from adulthood to old and very old age. Recent longitudinal analyses suggest that changes in sensory and intellectual functioning are interrelated. Experimental studies investigate the interdependence between cognitive and sensory/sensorimotor aging by examining the effects of simulated sensory loss on cognitive performance, or the effects of cognitive load manipulations on sensory or motor performance. Generally, both types of manipulations hinder older adults' performance more than that of younger adults. Theoretically, the age-associated intensification of the links among sensory, sensorimotor and cognitive functions observed both correlationally and experimentally may point to (a). common causes influencing all three functions; (b). an increase in resource overlap, cross-domain resource competition, and compensatory tradeoffs; and (c). a combination of the two. Future research aiming at discerning the relative import of these possibilities would profit from an integration of experimental and correlational research strategies.     

Reevaluation of motor cortex and of sensorimotor overlap in cerebral cortex of albino rats

The organization of motor cortex and the sensorimotor overlap zone was examined by in-depth electrical stimulation using micromapping procedures in rats. The cutaneous somatic sensory, as well as the efferent motor projections to the hindlimb and forelimb sensorimotor overlap zone were studied in the same animals. Low-threshold movements were elicited from protions of 3 architectonic areas: the lateral agranular, dysgranular and granular areas. Cutaneous light touch projections occur only within the granular area. Cutaneous projections to, and motor projections from individual punctures in the granular overlap zone did not always involve homologous body parts. The total motor cortex exhibits a general musculotopic pattern of organization.     

Interactions of the superior colliculus and the sensorimotor cortex in the alert rabbit]

The tonic increased influence of the superior colliculus (SC) on the formation of visual responses of the sensorimotor cortex (SMC) was shown on the alert rabbits. It was shown that SC influence was realized through tectothalamocortical (nucleus lateralis posterior) canal relation. It was established that SMC of the alert rabbits in its turn exerts the inhibitory phasic influence on SC function. The obtained data are discussed in the light of participation of the colliculo-cortical and cortico-collicular interactions in the organization of the visual-motor coordination necessary for realization of the visual controlled behaviour.     

Norepinephrine depletion impairs motor recovery following sensorimotor cortex injury in the rat

Beam-walking in the rat provides a method for investigating the effects of drugs on motor recovery following unilateral injury to the sensorimotor cortex. In the present experiment, the impact of norepinephrine depletion on beam-walking recovery was investigated. Groups of rats were first given either the neurotoxin DSP-4 or saline. Two weeks later, the animals were trained at the beam-walking task. Rats were then subjected to either a unilateral sensorimotor cortex lesion or sham operation. Recovery of beam-walking performance was measured over the next 12 days. Pretreatment with DSP-4 significantly slowed the rate of recovery but did not significantly affect sham-operated rats. Norepinephrine was significantly diminished in both lesioned and sham-operated rats that had been given DSP-4. These results are consistent with the hypothesis that recovery of beam-walking in the rat is mediated, at least in part, through noradrenergic neurons.     

Multiple synapse formation in the motor cortex opposite unilateral sensorimotor cortex lesions in adult rats.

Unilateral damage to the forelimb region of the sensorimotor cortex (FLsmc) in adult rats has previously been found to result in dendritic growth and synaptogenesis in layer V of the contralateral motor cortex. The neuronal growth appears to be mediated in part by lesion-induced changes in the use of the forelimbs. Whether these neuronal changes involve alterations in the structure and/or configuration of synaptic connections in layer V has not previously been investigated. The present study used stereological measures to characterize structural alterations in axonal processes and synaptic connections using electron micrographs generated in a previous study of the motor cortex contralateral to FLsmc lesions. Of primary interest were synapses formed by multiple synaptic boutons (MSBs), which have recently been found to be a major component of experience-related neocortical plasticity, and synapses with perforated postsynaptic densities (PSDs), which are putatively associated with enhanced synaptic efficacy. In comparison with sham-operated rats, there was an increase in the proportion and ratio of synapses to neurons formed by MSBs and in synapses with perforated PSDs at 30 days after the lesions. Furthermore, perforated synapses formed by MSBs were markedly increased at 18 and 30 days after the lesion in comparison with sham-operated rats. Preceding these synaptic structural changes (at 10 days postlesion), myelinated axons were reduced in volume fraction and volume per neuron in comparison with sham-operated rats but returned to normal levels at subsequent time points. These results are consistent with a lesion-induced degeneration and subsequent sprouting of axons. Together, these data indicate that a major restructuring of synaptic connectivity occurs in the cortex opposite FLsmc lesions in adult animals. This lesion-induced restructuring may be guided by ongoing changes in the use of the forelimbs.     

Interactions between the cannabinoid and dopaminergic systems: evidence from animal studies

There is a prominent role of the cannabinoid system to control basal ganglia function, in respect to reward, psychomotor function and motor control. Cannabinoid dysregulations might have a pathogenetic role in dopamine- and basal ganglia related neuropsychiatric disorders, such as drug addiction, psychosis, Parkinson's disease and Huntington's disease. This review highlights interactions between cannabinoids, and dopamine, to modulate neurotransmitter release and synaptic plasticity in the context of drug addiction, psychosis and cognition. Modulating endocannabinoid function, as a plasticity based therapeutic strategy, in the above pathologies with particular focus on cannabinoid receptor type 1 (CB1 receptor) antagonists/inverse agonists, is discussed. On the basis of the existing literature and of new experimental evidence presented here, CB1 receptor antagonists might be beneficial in disease states associated with hedonic dysregulation, and with cognitive dysfunction in particular in the context of psychosis. It is suggested that this effects might be mediated via a hyperglutamatergic state through metabotropic glutamate activation. Indications for endocannabinoid catabolism inhibitors in psychiatric disorders, that might be CB1 receptor independent and might involve TRPV1 receptors, are also discussed.     

Genetic evidence for cognitive reserve: variations in memory and related cognitive functions

Variations in cognitive functions across individuals are observed universally, and such observations serve as the basis of cognitive reserve (CR). Broadly, cognitive reserve refers to the inconsistency between neuropathology and clinical severity. The causes of such individual variations are likely to be multi-factorial. In this review, I present studies which suggest that genes are likely to be the contributing causes, and these genes interact with environmental factors to produce even greater variations in cognitive functions. A number of animal and human studies are beginning to reveal the role of genetic contributions to cognitive functions like memory, memory decline, general intelligence, and language. Twin studies suggest that there is a substantial heritable component for memory and related cognitive functions, such as general intelligence and language, but not for others. Thus, heritability estimates vary by cognitive domain. Animal studies and some human studies have identified genes or candidate loci that contribute to memory as well as other related cognitive phenotypes. Yet, our current understanding is limited. It will require interdisciplinary efforts from a number of different fields to better define the neuropsychological phenotype. At the same time, it is necessary to take into account both genetic and environmental factors to understand the complex network underlying CR.     

Somatosensory and motor representations in cerebral cortex of a primitive mammal (Monodelphis domestica): a window into the early evolution of sensorimotor cortex

To examine the potential early stages in the evolution of sensorimotor cortex, electrophysiological studies were conducted in the primitive South American marsupial opossum, Monodelphis domestica. Somatosensory maps derived from multiunit microelectrode recordings revealed a complete somatosensory representation of the contralateral body surface within a large region of midrostral cortex (primary somatosensory cortex, or S1). A large proportion ( approximately 51%) of S1 was devoted to representation of the glaborous snout, mystacial vibrissae, lower jaw, and oral cavity (the rostrum). A second representation, the second somatosensory area (or S2), was found adjacent and caudolateral to S1 as a mirror image reversed along the representation of the glabrous snout. A reversal of somatotopic order and an enlargement of receptive fields marked the transition from S1 to S2. Mapping of excitable cortex was conducted by using intracortical microstimulation (ICMS) techniques, as well as low-impedance depth stimulation and bipolar surface stimulation. In all three procedures, electrical stimulation resulted in movements confined strictly to the face. Specifically, at virtually all sites from which movements could be evoked, stimulation resulted in only vibrissae movement. ICMS-evoked vibrissae movements typically occurred at sites within S1 with receptive fields of the mystacial vibrissae, lower jaw, and glaborous snout. Results were similar using low-impedance depth stimulation and bipolar surface stimulation techniques except that the motor response maps were generally larger in area. There was no evidence of a motor representation rostral to S1. Examination of the cytoarchitecture in this cortical region (reminiscent of typical mammalian somatosensory cortex) and the high levels of stimulation needed for vibrissae movement suggest that the parietal neocortex of Monodelphis is representative of a primitive sensorimotor condition. It possesses a complete S1 representation with an incomplete motor component overlapping the S1 representation of the face. It contains no primary motor representation. Completion of the motor representations within S1 (trunk, limbs, tail) as well as the emergence of a primary motor cortex rostral to S1 may have occurred relatively late in mammalian phylogeny.     

Contribution of writing to reading: Dissociation between cognitive and motor process in the left dorsal premotor cortex

Functional brain imaging studies reported activation of the left dorsal premotor cortex (PMd), that is, a main area in the writing network, in reading tasks. However, it remains unclear whether this area is causally relevant for written stimulus recognition or its activation simply results from a passive coactivation of reading and writing networks. Here, we used chronometric paired‐pulse transcranial magnetic stimulation (TMS) to address this issue by disrupting the activity of the PMd, the so‐called Exner's area, while participants performed a lexical decision task. Both words and pseudowords were presented in printed and handwritten characters. The latter was assumed to be closely associated with motor representations of handwriting gestures. We found that TMS over the PMd in relatively early time‐windows, i.e., between 60 and 160 ms after the stimulus onset, increased reaction times to pseudoword without affecting word recognition. Interestingly, this result pattern was found for both printed and handwritten characters, that is, regardless of whether the characters evoked motor representations of writing actions. Our result showed that under some circumstances the activation of the PMd does not simply result from passive association between reading and writing networks but has a functional role in the reading process. At least, at an early stage of written stimuli recognition, this role seems to depend on a common sublexical and serial process underlying writing and pseudoword reading rather than on an implicit evocation of writing actions during reading as typically assumed. Hum Brain Mapp 37:1531‐1543, 2016. © 2016 Wiley Periodicals, Inc.     

The role of the premotor cortex and the primary motor cortex in action verb comprehension: evidence from Granger causality analysis

Although numerous studies find the premotor cortex and the primary motor cortex are involved in action language comprehension, so far the nature of these motor effects is still in controversy. Some researchers suggest that the motor effects reflect that the premotor cortex and the primary motor cortex make functional contributions to the semantic access of action verbs, while other authors argue that the motor effects are caused by comprehension. In the current study, we used Granger causality analysis to investigate the roles of the premotor cortex and the primary motor cortex in processing of manual-action verbs. Regions of interest were selected in the primary motor cortex (M1) and the premotor cortex based on a hand motion task, and in the left posterior middle temporal gyrus (lexical semantic area) based on the reading task effect. We found that (1) the left posterior middle temporal gyrus had a causal influence on the left M1; and (2) the left posterior middle temporal gyrus and the left premotor cortex had bidirectional causal relations. These results suggest that the premotor cortex and the primary motor cortex play different roles in manual verb comprehension. The premotor cortex may be involved in motor simulation that contributes to action language processing, while the primary motor cortex may be engaged in a processing stage influenced by the meaning access of manual-action verbs. Further investigation combining effective connectivity analysis and technique with high temporal resolution is necessary for better clarification of the roles of the premotor cortex and the primary motor cortex in action language comprehension.     

Altered connectivity between prefrontal and sensorimotor cortex in conversion paralysis

Conversion paralysis (CP) is a frequent and impairing psychiatric disorder, affecting voluntary motor function. Yet, we have previously shown that the motor system of CP patients with a unilateral conversion paresis is recruited to a similar degree during imagined movements of the affected and unaffected limb. In contrast, imagery of movements with the affected limb results in larger prefrontal activation. It remains unclear how this hand-specific increased prefrontal activity relates to the reduced responsiveness of motor and somatosensory areas, a consistent and important feature of CP patients.In the current study, we investigated changes in the inter-regional coupling between prefrontal cortex (PFC) and sensorimotor regions when CP patients imagined movements involving either the affected or the unaffected hand. We found that there were distinct connectivity patterns for different parts of the PFC. While ventromedial PFC was not functionally connected to the motor system, we observed strong functional coupling between the dorsolateral PFC and various sensorimotor areas. Furthermore, this coupling was modulated by whether patients imagined movements of their affected or unaffected hand. Together, these results suggest that the reduced motor responsitivity observed in CP may be linked to altered dorsolateral prefrontal-motor connectivity.     

Infant motor development and adult cognitive functions in schizophrenia

BACKGROUND: Childhood neuromotor dysfunction is a risk factor for schizophrenia, a disorder in which cognitive deficits are prominent. The relationship between early neurodevelopment and adult cognition in schizophrenia remains unclear. METHODS: We examined the associations between infant motor development and adult cognitive functions in schizophrenia (n = 61) and the general population (n = 104) in a sample drawn from the The Northern Finland 1966 Birth Cohort. Data on ages of learning to stand and walk with or without support were obtained at age 12 months by health visitor assessment. Neurocognitive measures at age 33-35 included executive function, verbal and visual episodic memory, and visuo-spatial working memory. RESULTS: The schizophrenia group achieved neuromotor milestones later and performed significantly worse than the control group on all measures of cognition. In pooled analyses there were associations between infant motor development and adult cognition in the domains of executive function, verbal learning and visuospatial working memory, but not in visual object learning. The pattern of associations between development and cognition was similar in schizophrenia and the general population. CONCLUSIONS: These findings are consistent with the hypothesis that in schizophrenia mild infant motor developmental delay and adult cognitive deficits (at least in some domains) are age dependent manifestations of the same underlying neural process. Thus, they may be better considered as part of a single longitudinal syndrome.     

Reduced sensorimotor inhibition in the ipsilesional motor cortex in a patient with chronic stroke of the paramedian thalamus.

OBJECTIVE: Unilateral or bilateral paramedian infarction in the region of the thalamus and upper midbrain may lead to hypersomnia. To determine whether unilateral infarction of the paramedian thalamus leads to changes in excitability of ipsilesional primary motor hand area (M1). METHODS: We describe a patient with chronic stroke of the right dorsomedian and intralaminar thalamic nuclei, who suffered from mild persistent hypersomnia. We studied the excitability of the right and left M1 with transcranial magnetic stimulation (TMS) in the patient, and in 10 healthy controls. RESULTS: In contrast to healthy controls, contralateral electrical stimulation of the median nerve failed to induce short-latency afferent inhibition (SAI) in the ipsilesional M1. Other measures of corticomotor excitability and somatosensory evoked potentials were normal. CONCLUSIONS: The selective loss of ipsilateral SAI in a patient with paramedian thalamic stroke suggests that during wakefulness, the intact paramedian thalamus facilitates the excitability of intracortical inhibitory circuits, which process thalamocortical sensory inputs in the ipsilateral M1. This preliminary finding suggests that measurements of SAI may provide a means of probing the integrity of some neural pathways, which are involved in the control of wakefulness and arousal. SIGNIFICANCE: In addition to the established role of the paramedian thalamus in arousal and memory, our observation suggests that thalamocortical projections from the paramedian thalamus contribute to the integration of sensory input at the cortical level during wakefulness.     

Modulation of motor cortex excitability by sustained peripheral stimulation: The interaction between the motor cortex and the cerebellum

The excitability of cortical neurons in the motor cortex is determined by their membrane potential and by the level of intracortical inhibition. The excitability of the motor cortex as a whole is a function of single cell excitability, synaptic strength, and the balance between excitatory cells and inhibitory cells. It is now established that a sustained period of somatosensory stimulation increases the excitability of motor cortex areas controlling muscles in those body parts that received the stimulation prior to excitability testing. So far, it has been supposed that the sensorimotor cortex was the anatomical substrate of these excitability changes, which could represent an early change in cortical network function before structural plasticity occurs. Recent experimental studies highlight that the cerebellum, especially the interpositus nucleus, plays a key role in the adaptation of the motor cortex to repeated trains of stimulation. Interpositus neurons, which receive inputs from both sensorimotor cortex and the spinal cord, are involved in somesthetic reflex behaviors and assist the cerebral cortex in transforming sensory signals to motor-oriented commands by acting via the cerebello-thalamo-cortical projections. Moreover, climbing fibers originating in the inferior olivary complex and innervating the nucleus interpositus mediate highly integrated sensorimotor information derived from spinal modules. It appears that the interpositus nucleus is a main subcortical modulator of the excitability changes occurring in the motor cortex, which may be a substrate of early plasticity effective in motor learning and recovery from lesion.