Motor control is a ubiquitous aspect of human function, and from its earliest origins, abnormal motor control has been proposed as being central to schizophrenia. The neurobiological architecture of the motor system is well understood in primates and involves cortical and sub-cortical components including the primary motor cortex, supplementary motor area, dorsal anterior cingulate cortex, the prefrontal cortex, the basal ganglia, and cerebellum. Notably all of these regions are associated in some manner to the pathophysiology of schizophrenia. At the molecular scale, both dopamine and γ-Aminobutyric Acid (GABA) abnormalities have been associated with working memory dysfunction, but particularly relating to the basal ganglia and the prefrontal cortex respectively. As evidence from multiple scales (behavioral, regional and molecular) converges, here we provide a synthesis of the bio-behavioral relevance of motor dysfunction in schizophrenia, and its consistency across scales. We believe that the selective compendium we provide can supplement calls arguing for renewed interest in studying the motor system in schizophrenia. We believe that in addition to being a highly relevant target for the study of schizophrenia related pathways in the brain, such focus provides tractable behavioral probes for in vivo imaging studies in the illness. Our assessment is that the motor system is a highly valuable research domain for the study of schizophrenia.

Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease that targets motor neurons. Upper motor neurons degeneration is pathologically characterized by brain iron accumulation. Signal attenuation in the shape of a ribbon at the posterior border of the precentral gyrus can be observed on conventional magnetic resonance imaging (MRI) sequences including T2-weighted sequence. Methods: With the aim to know the qualities of this potential marker of ALS, we conducted a prospective study. Patients with definite ALS in the age range of 40–70 years and healthy controls underwent 3T brain MRI using a standardized sequence. A second MRI was performed 18 months later under the same conditions in the patients with ALS. Results: Most of the patients with ALS (91.66%) exhibited a “black ribbon” (BR) with an average area of 79.98 mm3. Signal attenuation discriminated ALS with a mean value of 63.97 arbitrary units (AU) on the left BR (95% CI: 60.67–67.27), a mean value of 59.15 AU (95% CI: 54.78–63.53) on the right BR, and a significant difference with control subjects presenting a mean value of 107.85 AU (p < 0.001). The optimal cut-off point for differentiating patients with ALS from controls (sensitivity, 0.92; specificity, 0.93) was 83 AU. Forced vital capacity and muscle strength in the contralateral upper extremity were significantly correlated with the ribbon intensity in ALS. Patients who underwent a second study exhibited significant changes in the BR related to the rapid evolution of the disease. Conclusions: This marker represents a valuable tool for the selection of candidates and their follow-up in clinical trials.

Chorioamnionitis and intrauterine growth retardation (IUGR) are risk factors for cerebral palsy (CP). Common bacteria isolated in chorioamnionitis include group B Streptococcus (GBS) serotypes Ia and III. Little is known about the impact of placental inflammation induced by different bacteria, including different GBS strains. We aimed to test the impact of chorioamnionitis induced by two common GBS serotypes (GBSIa and GBSIII) on growth and neuromotor outcomes in the progeny. Dams were exposed at the end of gestation to either saline, inactivated GBSIa or GBSIII. Inactivated GBS bacteria invaded placentas and triggered a chorioamnionitis featured by massive polymorphonuclear cell infiltrations. Offspring exposed to GBSIII – but not to GBSIa – developed IUGR, persisting beyond adolescent age. Male rats in utero exposed to GBSIII traveled a lower distance in the Open Field test, which was correlating with their level of IUGR. GBSIII-exposed rats presented decreased startle responses to acoustic stimuli beyond adolescent age. GBS-exposed rats displayed a dysmyelinated white matter in the corpus callosum adjacent to thinner primary motor cortices. A decreased density of microglial cells was detected in the mature corpus callosum of GBSIII-exposed males – but not females – which was correlating positively with the primary motor cortex thickness. Altogether, our results demonstrate a causal link between pathogen-induced acute chorioamnionitis and (1) IUGR, (2) serotype- and sex-specific neuromotor impairments and (3) abnormal development of primary motor cortices, dysmyelinated white matter and decreased density of microglial cells.

This paper highlights major developments over the past two to three decades in the neuropsychology of movement and its disorders. We focus on studies in healthy individuals and patients, which have identified cognitive contributions to movement control and animal work that has delineated the neural circuitry that makes these interactions possible. We cover advances in three major areas: (1) the neuroanatomical aspects of the “motor” system with an emphasis on multiple parallel circuits that include cortical, corticostriate, and corticocerebellar connections; (2) behavioral paradigms that have enabled an appreciation of the cognitive influences on the preparation and execution of movement; and (3) hemispheric differences (exemplified by limb praxis, motor sequencing, and motor learning). Finally, we discuss the clinical implications of this work, and make suggestions for future research in this area. (JINS, 2017, 23, 768–777)

We present a model for several early stages of the sensorimotor transformations involved in targeted arm movement. In psychophysical experiments, human subjects pointed to the remembered locations of randomly placed targets in three-dimensional space. They made consistent errors in distance, and from these errors stages in the sensorimotor transformation were deduced. When subjects attempted to move the right index finger to a virtual target they consistently undershot the distance of the more distal targets. Other experiments indicated that the error was in the sensorimotor transformation rather than in the perception of distance. The error was most consistent when evaluated using a spherical coordinate system based at the right shoulder, indicating that the neural representation of target parameters is transformed from a retinocentric representation to a shoulder-centered representation. According to the model, the error in distance results from the neural implementation of a linear approximation in the algorithm to transform shoulder-centered target parameters into a set of arm orientations appropriate for placing the finger on the target. The transformation to final arm orientations places visually derived information into a frame of reference where it can readily be combined with kinesthetically derived information about initial arm orientations. The combination of these representations of initial and final arm orientations could give rise to the representation of movement direction recorded in the motor cortex by Georgopoulos and his colleagues. Later stages, such as the transformation from kinematic (position) to dynamic (force) parameters, or to levels of muscle activation, are beyond the scope of the present model.

To investigate neural mechanisms of movement, physiologists have analyzed the activity of task-related neurons in behaving animals. The relative onset latencies of neural activity have been scrutinized for evidence of a functional hierarchy of sequentially recruited centers, but experiments reveal that activity changes occur largely in parallel. Neurons whose activity covaries with movement parameters have been sought for evidence of explicit coding of parameters such as active force, limb displacement, and behavioral set. Neurons with recognizable relations to the task are typically selected from a larger population, ignoring those cells with complex relations to the task and unmodulated cells. Selective interpretations are also used to support the notion that different motor regions perform different motor functions; again, current evidence suggests that units with similar properties are distributed over widely different regions.

These coding issues are reexamined for premotoneuronal (PreM) cells, whose correlational links with motoneurons are revealed by spike-triggered averages. PreM cells are recruited over long times relative to their target muscles; they show diverse response patterns relative to the muscle force they produce; functionally disparate PreM cells such as afferent fibers and descending corticomotoneuronal and rubromotoneuronal cells can exhibit similar patterns. Neural mechanisms have been further elucidated by neural network simulations of sensorimotor behavior; the pre-output hidden units typically show diverse response patterns in relation to their target units. Thus, studies in which both the activity and the connectivity of the same units are known reveal that units with both simple and complex relations to the task contribute significantly to the output. This suggests that the search for explicit coding may be diverting us from understanding distributed neural mechanisms that operate without literal representations.

A previous study reported preliminary results of enhanced processing of simple visual information in the form of faster reaction times, in female fragile X premutation carriers (fXPCs). In this study, we assessed manual and oral motor reaction times in 30 female fXPCs and 20 neurotypical (NT) controls. Participants completed two versions of the reaction time task; one version required a manual motor response and the other version required an oral motor response. Results revealed that the female fXPCs displayed faster reaction times for both manual and oral motor responses relative to NT controls. Molecular measures including CGG repeat length, FMR1 mRNA levels, and age were not associated with performance in either group. Given previously reported age and CGG repeat modulated performance on a magnitude comparison task in this same group of premutation carriers, results from the current study seem to suggest that female fXPCs may have spared basic psychomotor functionality. (JINS, 2011, 17, 746–750)

Knowledge of the input-output characteristics of various neuronal types is a necessary first step toward an understanding of cellular events related to waking and sleep. In spite of the oversimplification involved, the dichotomy in terms of type I (long-axoned, output) neurons and type II (short-axoned, local) interneurons is helpful in functionally delineating the neuronal circuits involved in the genesis and epiphenomena of waking and sleep states. The possibility is envisaged that cortical interneurons, which are particularly related to higher neuronal activity and have been found in previous experiments to be more active during sleep than during wakefulness, might be involved in complex integrative processes occurring during certain sleep stages. Electrophysiological criteria for the identification of output cells and interneurons are developed, with emphasis on various possibilities and difficulties involved in recognizing interneurons of the mammalian brain. The high-frequency repetitive activity of interneurons is discussed, together with various possibilities of error to be avoided when interpreting data from bursting cells. Data first show opposite changes in spontaneous and evoked discharges of identified output cells versus putative interneurons recorded from motor and parietal association cortical areas in behaving monkeys and cats during wakefulness (W) compared to sleep with synchronized EEG activity (S): significantly increased rates of spontaneous firing, enhanced antidromic or synaptic responsiveness, associated with shorter periods of inhibition in type I (pyramidal tract, cortico-thalamic and cortico-pontine) cells during W versus significantly decreased frequencies of spontaneous discharge and depression of synaptically elicited reponses of type II cells during W compared to S. These findings are partly explained on the basis of recent iontophoretic studies showing that acetylcholine, viewed as a synaptic transmitter of the arousal system, excites output-type neurons and inhibits high-frequency bursting cells. Comparing W and S to the deepest stage of sleep with desynchronized EEG activity (D) in type I and type II cells revealed that: (a) the increased firing rates of output cells in D, over those in W and S, is substantially due to a tonic excitation during this state, and rapid eye movements (REMs) only contribute to the further increase of discharge frequencies; (b) in contrast, the increased rates of discharge in interneurons during D is entirely ascribable to REM-related firing. On the basis of experiments reporting that increased duration of D has beneficial effects upon retention of information acquired during W, the suggestion is made that increased firing rates of association cortical interneurons during REM epochs of D sleep are an important factor in maintaining the soundness of a memory trace.

On the basis of what is known about the neural circuitry essential or normally involved in eyeblink classical conditioning (EBCC), the pattern of neurodegeneration in Huntington's disease (HD) would not appear to interfere with this type of learning. HD causes severe atrophy of the basal ganglia and thinning and shrinkage of the cerebral cortex. However, the hippocampus and hippocampal cholinergic system remain relatively intact, as does the cerebellum. Because the brain circuitry engaged in EBCC is neither lesioned nor disrupted in HD, it was predicted that HD patients would perform like normal control subjects in the 400-ms delay EBCC paradigm. Performance of seven patients with HD was compared to age-matched normals, with two control subjects matched to each HD patient. There were no differences in production of conditioned responses (CRs) between HD patients and normal control subjects, but the timing of the CR was abnormal in HD. Comparisons of HD patients to patients with other neurodegenerative diseases (probable Alzheimer's disease (PAD) and Down syndrome (DS) over the age of 35 with presumed Alzheimer-like neuropathology) and to patients with cerebellar lesions demonstrated significantly better EBCC performance in HD. Results suggest that the ability to acquire CRs is normal in HD, but the striatum may have some role in optimizing the timing of the CR. (JINS, 1996, 2, 323–334.)

The influence of action knowledge associated with novel objects was investigated using functional magnetic resonance imaging. Participants were trained on complex actions associated with novel objects (“tools”) and had experience manipulating other visually similar novel objects (“shapes”). During scanning, participants viewed, imagined grasping, and imagined using the objects. Based on previous neuroimaging and neuropsychological findings, our primary goal was to examine frontal and parietal regions subserving action representations associated with visual objects, namely the left inferior parietal lobule (IPL), the left ventral premotor cortex (VPM) and the presupplementary motor cortex (pre-SMA). We predicted differences between the tool and shape stimuli, modulated also by task demands. In viewing, we found greater effect sizes in the left VPM and IPL for tools versus shapes. In grasping, there was similar activation with both object types. The largest differences existed in using, in which greater effect sizes were found for tools versus shapes in left IPL and pre-SMA, and marginally in the left VPM. We suggest that representations of tools extend beyond classically defined affordances and recruit processing about both graspability and known action plans in tasks involving visual memory, motor imagery, and motor execution. (JINS, 2007, 13, 1009–1020.)

This study utilised a finger force task to investigate the influence of attention and age on the occurrence of motor overflow in the form of mirror movements in neurologically intact adults. Forty right-handed participants were recruited from three age groups: 20–30 years, 40–50 years, and 60–70 years. Participants were required to maintain a target force using both their index and middle fingers, representing 50% of their maximum strength capacity for that hand. Attention was directed to a hand by activating a bone conduction vibrator attached to the small finger of that hand. Based on Cabeza's (2002) model of hemispheric asymmetry reduction in older adults, it was hypothesised that mirror movements would increase with age. Furthermore, it was expected that when the attentional demands of the task were increased, motor overflow occurrence would be exacerbated for the older adult group. The results obtained provide support for the model, and qualified support for the hypothesis that increasing the attentional demands of a task results in greater motor overflow. It is proposed that the association between mirror movements and age observed in this study may result from an age-related increase in bihemispheric activation that occurs in older adults, who, unlike younger adults, benefit from bihemispheric processing for task performance. (JINS, 2005, 11, 855–862.)

Cerebro–cerebellar interactions are becoming progressively more focused in their anatomical substrate but their functional meaning is still elusive. Here, we review current data on the cerebellar influence on cortical function, with special emphasis on the importance of the cerebellar input for cortical processing in primary motor and sensorimotor areas. Differences in the intracortical processing of cerebellar information are described and the possible role of the thalamus in controlling cerebro–cerebellar loops discussed.

The present study was aimed at deciphering whether the delay in choice reaction time (RT) and the silent period (SP) caused by transcranial magnetic stimulation (TMS) of the motor cortex in the ongoing electromyogram are due to the same physiological mechanism. To this end, the effect of TMS was studied in 6 healthy volunteers performing a between-hand choice RT task. Specific predictions were derived from a logic inspired from the “postponed stages” hypothesis (Pashler & Johnson, 1989). This logic predicts a correlation between SP duration and RT when the stimulated cortex is involved in the response, and a stronger correlation when the stimulation is delivered later during the RT interval. The effect of TMS on RT was twofold: At early stimulation times, the stimulation shortened the RT and this effect was independent of the involvement of the stimulated motor cortex in the subsequent response. At later stimulation times, TMS had a disruptive effect, provided that the stimulated cortex was involved in the response. When the stimulated cortex was involved in the response, there was a correlation between SP and RT; this correlation was stronger when the stimulation occurred later. In contrast, there was no correlation between these two variables when the stimulated cortex was not involved.

The ultrastructure of Betz cells in the 5th layer of the primary motor cortex of 17 neurologically and psychiatrically normal control individuals was studied. Normal-appearing Betz cells showed a wide range of features including novel electron-dense inclusion bodies (Bunina-like bodies) resembling Bunina bodies characteristic of amyotrophic lateral sclerosis (ALS), accumulations of neurofilaments (10 nm in diameter), bundles of filaments (20–25 nm in diameter) thicker than neurofilaments, lamellar structures, lamellar bodies and structures similar to Hirano bodies. Among these ‘abnormal’ features, the presence of Bunina-like bodies may be an age-related nonspecific degenerative change, since they appeared more frequently in elderly individuals. The presence of these abnormal features—particularly the Bunina-like bodies—in the Betz cells of normal human brains must be considered in the assessment of the pathognomonic significance of such structures in ALS and other neurological diseases that affect the motor cortex.