Subcortical Motor Structures Research Articles

Modification of Brain Functional Connectivity in Adolescent Thoracic Idiopathic Scoliosis by Lower Extremities Position

The involvement of the brain motor system in idiopathic scoliosis remains unclear. In this paper, we question whether the functional connectivity (FC) of the central motor circuitry is abnormal in adolescent idiopathic scoliosis (AIS) and whether it can be modified by flexion of the lower extremities. Functional magnetic resonance imaging (fMRI) in 18 patients with a right thoracic idiopathic curve greater than 30° (mean angle 49.4°, mean age 15.3 years, 4 males) and 22 healthy controls (mean age 18.2 years, 4 males) was explored using a 3T MR scanner. We measured their resting-state fMRI: (a) with extended lower extremities; (b) with semiflexion of the left lower extremity and extended right lower extremity, with hip abduction. Decreased FC between the secondary motor area (SMA) and postcentral cortex, pallidum and cuneus, postcentral gyrus and cerebellum, putamen and temporal lateral neocortex was observed in AIS. This pathological connectivity was reversed by lower extremity semiflexion. The FC between cortical and subcortical motor structures is significantly decreased in AIS. The decreased FC of the SMA, basal ganglia, cuneus (a hub structure), and cerebellum indicates the functional impairment of structures involved in regulating muscular tone. FC impairment in patients with AIS appears to be a reaction to the pathological condition. This pathological pattern flexibly reacts to changes in the positioning of the lower extremities, showing that the functional impairment of brain motor circuitry in AIS is reversible. We suggest that the reactivity of cerebral activity leading to brain activity normalization could be used for a rehabilitation program for patients with AIS.

Association of Genetic Variant Linked to Hemochromatosis With Brain Magnetic Resonance Imaging Measures of Iron and Movement Disorders

Hereditary hemochromatosis (HH) is an autosomal recessive genetic disorder that leads to iron overload. Conflicting results from previous research has led some to believe the brain is spared the toxic effects of iron in HH. To test the association of the strongest genetic risk variant for HH on brainwide measures sensitive to iron deposition and the rates of movement disorders in a substantially larger sample than previous studies of its kind. This cross-sectional retrospective study included participants from the UK Biobank, a population-based sample. Genotype, health record, and neuroimaging data were collected from January 2006 to May 2021. Data analysis was conducted from January 2021 to April 2022. Disorders tested included movement disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10], codes G20-G26), abnormalities of gait and mobility (ICD-10 codes R26), and other disorders of the nervous system (ICD-10 codes G90-G99). Homozygosity for p.C282Y, the largest known genetic risk factor for HH. T2-weighted and T2* signal intensity from brain magnetic resonance imaging scans, measures sensitive to iron deposition, and clinical diagnosis of neurological disorders. The total cohort consisted of 488 288 individuals (264 719 female; ages 49-87 years, largely northern European ancestry), 2889 of whom were p.C282Y homozygotes. The neuroimaging analysis consisted of 836 individuals: 165 p.C282Y homozygotes (99 female) and 671 matched controls (399 female). A total of 206 individuals were excluded from analysis due to withdrawal of consent. Neuroimaging analysis showed that p.C282Y homozygosity was associated with decreased T2-weighted and T2* signal intensity in subcortical motor structures (basal ganglia, thalamus, red nucleus, and cerebellum; Cohen d >1) consistent with substantial iron deposition. Across the whole UK Biobank (2889 p.C282Y homozygotes, 485 399 controls), we found a significantly increased prevalence for movement disorders in male homozygotes (OR, 1.80; 95% CI, 1.28-2.55; P = .001) but not female individuals (OR, 1.09; 95% CI, 0.70-1.73; P = .69). Among the 31 p.C282Y male homozygotes with a movement disorder, only 10 had a concurrent HH diagnosis. These findings indicate increased iron deposition in subcortical motor circuits in p.C282Y homozygotes and confirm an increased association with movement disorders in male homozygotes. Early treatment in HH effectively prevents the negative consequences of iron overload in the liver and heart. Our work suggests that screening for p.C282Y homozygosity in high-risk individuals also has the potential to reduce brain iron accumulation and to reduce the risk of movement disorders among male individuals who are homozygous for this mutation.

Deep Brain Stimulation of the Pedunculopontine Tegmental Nucleus (PPN) Influences Visual Contrast Sensitivity in Human Observers.

The parapontine nucleus of the thalamus (PPN) is a neuromodulatory midbrain structure with widespread connectivity to cortical and subcortical motor structures, as well as the spinal cord. The PPN also projects to the thalamus, including visual relay nuclei like the LGN and the pulvinar. Moreover, there is intense connectivity with sensory structures of the tegmentum in particular with the superior colliculus (SC). Given the existence and abundance of projections to visual sensory structures, it is likely that activity in the PPN has some modulatory influence on visual sensory selection. Here we address this possibility by measuring the visual discrimination performance (luminance contrast thresholds) in a group of patients with Parkinson’s Disease (PD) treated with deep-brain stimulation (DBS) of the PPN to control gait and postural motor deficits. In each patient we measured the luminance-contrast threshold of being able to discriminate an orientation-target (Gabor-grating) as a function of stimulation frequency (high 60Hz, low 8/10, no stimulation). Thresholds were determined using a standard staircase-protocol that is based on parameter estimation by sequential testing (PEST). We observed that under low frequency stimulation thresholds increased relative to no and high frequency stimulation in five out of six patients, suggesting that DBS of the PPN has a frequency-dependent impact on visual selection processes at a rather elementary perceptual level.

The Ability to Move to a Beat Is Linked to the Consistency of Neural Responses to Sound

The ability to synchronize movement to a steady beat is a fundamental skill underlying musical performance and has been studied for decades as a model of sensorimotor synchronization. Nevertheless, little is known about the neural correlates of individual differences in the ability to synchronize to a beat. In particular, links between auditory-motor synchronization ability and characteristics of the brain's response to sound have not yet been explored. Given direct connections between the inferior colliculus (IC) and subcortical motor structures, we hypothesized that consistency of the neural response to sound within the IC is linked to the ability to tap consistently to a beat. Here, we show that adolescent humans who demonstrate less variability when tapping to a beat have auditory brainstem responses that are less variable as well. One of the sources of this enhanced consistency in subjects who can steadily tap to a beat may be decreased variability in the timing of the response, as these subjects also show greater between-trial phase-locking in the auditory brainstem response. Thus, musical training with a heavy emphasis on synchronization of movement to musical beats may improve auditory neural synchrony, potentially benefiting children with auditory-based language impairments characterized by excessively variable neural responses.

Hypothalamic Histaminergic and Orexinergic Modulation on Cerebellar and Vestibular Motor Control

Somatic-nonsomatic integration is critical for generation and execution of an appropriate and coordinated behavioral response to changes in internal and external environments. However, the underlying neural substrates and mechanisms are still enigmatic. Intriguingly, the central histaminergic and orexinergic systems originating from the hypothalamus, a high autonomic regulatory center, innervate almost the whole brain including various subcortical motor structures, particularly the cerebellum and vestibular nuclei. Here, we suggest that the hypothalamic histaminergic and orexinergic system bridging the nonsomatic center to somatic motor structures may actively modulate the cerebellar and vestibular nuclear neurons and subsequently participate in motor control and somatic-nonsomatic integration.

Blood natural killer cell cytotoxicity enhancement correlates with an increased activity in brain motor structures following chronic stimulation of the bed nucleus of the stria terminalis in rats

The present study indicates that a chronic 14 day electrical stimulation of the bed nucleus of the stria terminalis (BST) increased blood but not spleen natural killer cell (NK) cytotoxicity and a large granular lymphocyte (LGL) number. These immune changes positively correlated with the increased activity in brain cortical and subcortical motor structures that influence the BST stimulation-induced behavioral response. No significant changes in blood and spleen leukocyte population numbers and plasma corticosterone concentration after the stimulation were found. The obtained results suggest that this immunoenhancing effect on blood NK cell function and number is dependent on the behavioral outcome of the BST stimulation rather than endocrine response.

A knock-in reporter mouse model for Batten disease reveals predominant expression of Cln3 in visual, limbic and subcortical motor structures

Juvenile neuronal ceroid lipofuscinosis (JNCL) or Batten disease is an autosomal recessive neurodegenerative disorder of children caused by mutation in CLN3. JNCL is characterized by progressive visual impairment, cognitive and motor deficits, seizures and premature death. Information about the localization of CLN3 expressing neurons in the nervous system is limited, especially during development. The present study has systematically mapped the spatial and temporal localization of CLN3 reporter neurons in the entire nervous system including retina, using a knock-in reporter mouse model. CLN3 reporter is expressed predominantly in post-migratory neurons in visual and limbic cortices, anterior and intralaminar thalamic nuclei, amygdala, cerebellum, red nucleus, reticular formation, vestibular nuclei and retina. CLN3 reporter in the nervous system is mainly expressed during the first postnatal month except in the dentate gyrus, parasolitary nucleus and retina, where it is still strongly expressed in adulthood. The predominant distribution of CLN3 reporter neurons in visual, limbic and subcortical motor structures correlates well with the clinical symptoms of JNCL. These findings have also revealed potential target brain regions and time periods for future investigations of the disease mechanisms and therapeutic intervention.

What is adapted in saccadic adaptation?

What is adapted in saccadic adaptation?

The effects of a startle on the sit-to-stand manoeuvre

Simple ballistic movements are executed faster in reaction time task paradigms when the imperative signal (IS) is accompanied by a startling auditory stimulus (SAS). We examined whether this effect also occurs in complex movements such as the sit-to-stand manoeuvre (STS). Nine healthy volunteers performed STS to visual IS, either presented alone (control trials) or together with SAS (test trials). Reaction time, measured as the time between IS and take-off (TO), was significantly shortened in test trials when SAS was applied at an interval of 0 ms with respect to IS. The onset latency of EMG bursts recorded from tibialis anterior, lumbar paraspinal, quadriceps and biceps femoris muscles reduced proportionally to the shortening of TO. However, these effects were not observed if SAS was delivered 150 ms after IS, when the manoeuvre had already started. Our results suggest that stimuli acting on subcortical motor structures speed-up but do not otherwise interfere with the execution of the motor programs underlying the STS manoeuvre.

Excitability of subcortical motor circuits in Go/noGo and forced choice reaction time tasks

The size of the response to a startling auditory stimulus (SAS) may reflect the excitability of the reticulospinal tract. In this study, we examined whether there was any excitability change in the reticulospinal tract during preparation for execution of two types of choice reaction time task: a forced choice reaction time task (fCRT) and a Go/no-Go task (GnG). In 13 healthy volunteers we used three types of trials: control trials in which subjects were requested to perform ballistic wrist movements during fCRT or GnG tasks; test trials in which a SAS was presented with the visual cue, and baseline trials in which SAS was presented alone. Latency and area of the responses to SAS were measured in the orbicularis oculi and in the sternocleidomastoid (SCM) muscles. The results obtained in baseline trials were used to calculate the mean resting baseline excitability level of the reticulospinal tract for each individual, and the values obtained in test trials were expressed as percentages of mean baseline for normalization of data from all individuals. The area of the responses to SAS in SCM was significantly larger in fCRT than in GnG ( p = 0.002). There was a significant shortening of reaction time in test trials that was inversely correlated with area of SCM ( p < 0.05). We conclude that the subcortical motor tracts activated by SAS are more excitable during fCRT tasks than GnG tasks. Changing the excitability of subcortical motor structures may be a strategy used by the central nervous system in motor control that is selected according to the motor program.

Subcortical reorganization in amyotrophic lateral sclerosis

The cerebral cortex reorganizes in response to central or peripheral lesions. Although basal ganglia and cerebellum are key components of the network dedicated to movement control, their role in motor reorganization remains elusive. We therefore tested if slowly progressive neurodegenerative motor disease alters the subcortical functional anatomy of the basal ganglia-thalamo-cerebellar circuitry. Ten patients with amyotrophic lateral sclerosis (ALS) and ten healthy controls underwent functional magnetic resonance imaging (fMRI), while executing a simple finger flexion task. Cued by an acoustic trigger, they squeezed a handgrip force transducer with their right hand at 10% of their maximum voluntary contraction force. Movement frequency, amplitude, and force were controlled. Statistical parametric mapping of task-related BOLD-response revealed increased activation in ALS patients as compared to healthy controls. The main activation increases were found in the supplementary motor area, basal ganglia, brainstem, and cerebellum. These findings suggest that degeneration of cortical and spinal motor neurons in ALS leads to a recruitment of subcortical motor structures. These subcortical activation patterns strongly resemble functional activation in motor learning and might therefore represent adaptations of cortico-subcortical motor loops as a - albeit finally ineffective - mechanism to compensate for the ongoing loss of motor neurons in ALS.

SPECT abnormalities in generalized dystonia

A patient with severe, generalized dystonia and 6 age range-matched controls were studied with the regional cerebral blood flow tracer technetium-99m hexamethylpropyleneamine oxime by single-photon emission computed tomography to test the hypothesis that cerebellar function is abnormal in dystonia. Analysis was performed by drawing regions of interest around the caudate head nuclei, hemithalami, deep cerebellar nuclei, and cerebellar hemicortices. The counts in each region of interest were normalized to whole brain cerebral blood flow in an identical manner for each subject. The dystonic patient had a difference in regional cerebral blood flow between the right and left deep cerebellar nuclei, increased regional cerebral blood flow in subcortical motor structures, and an abnormal relationship between right cerebellar cortical and right deep cerebellar nuclear regional cerebral blood flow. The findings in this patient provide evidence that the cerebellum may play a role in the pathophysiology of motor signs in some patients with dystonia.

The gestural and temporal organization of assimilation

Ever since Wang and Fillmore [J. Speech Hear. Res. 4, 130 (1961)] phoneticians have distinguished between nonpredictable language‐specific speech habits and predictable universal articulatory constraints, the former being cortical and extrinsic to the vocal tract, the latter intrinsic to the vocal tract and the consequence of articulation mechanics. Assimilation came to be seen as an intrinsic vocal tract process, explained in terms of Öhman’s model of coarticulation [ 151 (1966)]. This contrasts with classical phonetics where assimilation is the result of preplanned reorganization of articulation. The work reported in this paper favors the classical view. Gestures involved in an assimilation are initiated earlier, delayed, or are held longer, than in nonassimilated situations. It is argued that this revision of gesture timing in relation to adjacent activity is an expression of preplanning of motor commands that takes place in the cortex where there is access to larger portions of the utterance (the subcortical motor structures have limited access and cannot advance or delay gestures). Examples of palatalization of Bulgarian apico‐alveolar stops and Swedish palatovelar stops are presented. The data are analyzed from x‐ray motion films by procedures described by Wood [J. Phon. 19, 281 (1991)].

Mutismus bei zentralmotorischen Störungen - Eine Literaturübersicht

Mutism can be defined as "a condition in which there is no, or very little, oral-verbal expression, whereas comprehension of speech ... is normal or at least at a considerably higher level" (Lebrun, 1990). Benson (1979) enumerates five neuroanatomical correlates of mutism: (a) damage to the Broca region, (b) lesion of the supplementary motor area of the dominant hemisphere, (c) dysfunction of the mesencephalic reticular system, (d) thalamotomy, and (e) bilateral pathology of cortical and subcortical motor structures. The last item refers to syndromes of mutism resulting from central motor disorders. Depending on location and size of the lesion this pathophysiological interpretation should hold true for the fourth point as well. In mutism due to central motor disturbances lacking verbal expression represents the most severe degree of dysarthria, i.e. anarthria. The present review provides a detailed description of mutism following corticobulbar, striatal, and cerebellar dysfunctions.

Ideomotor Apraxia in Huntington's Disease

The pattern of movement errors in ideomotor apraxia suggests an abnormality in selection and sequencing of component movements. Individuals with Huntington's disease were evaluated prospectively for the presence of apraxia, and aspects of motor and cognitive function were correlated with apraxic errors. Based on a conservative apraxia rating, ideomotor apraxia occurred in three (33%) of nine patients with a mean duration of disease of 10.4 years. Only two (22%) individuals made no apraxic errors, however, and the group as a whole made apraxic errors in 26% of movements. Apraxia was associated with errors in imitation of nonsymbolic movements but not with errors in recognition of gestures. It correlated significantly with duration of disease and with progressive abnormalities of posture but not with other individual aspects of elementary motor or cognitive function. These associations indicate that apraxia in Huntington's disease may be due primarily to involvement of subcortical motor structures rather than cerebral cortex.

Characteristics of motor potentials on impairment of the function of subcortical human brain motor structures

We have investigated the characteristics of motor potentials (MPs) in patients with impaired function of subcortical motor structures of the brain, causing symptoms of parkinsonism. We have isolated the MP components that precede movement, such as "the readiness potential" (N1), "the motor potential" (N2), and MP components which are electrophysiological correlates of processes of execution (P2 component) and of completion (N3 component) of movement. We established that in parkinsonism patients the MPs are changed compared to the normal; the most significant changes were observed in components N1, P2, and N3 as shown by a prolongation and certain decrease in the amplitude of these components. Component N2, regarded to be an electrophysiological correlate, reflecting the triggering of movement, has amplitude-time related parameters that are the most similar to the normal. We believe that this component is of cortical origin.

Topographical organization of the afferent connections of the principal ventromedial thalamic nucleus in the cat

The afferent connections to the principal division of the ventromedial thalamic nucleus (VMP) were studied in the cat by means of the HRP retrograde transport technique. The large (40 nl) and small (20 nl) injections of this enzyme were delivered into the VMP using different stereotaxic approaches. The main afferents to VMP emanated bilaterally from the prefrontal, premotor, and rostral agranular insular cortices. Another important group of afferents to the VMP were those originating in the rostral third of the reticular thalamic nucleus, the entopeduncular nucleus, the substantia nigra pars reticulata, and the deep cerebellar nuclei. From the cerebellar nuclei, the contralateral lateral nucleus and the caudal third of both (ipsi and contralateral) medial cerebellar nuclei were the origin of afferents to the VMP. Other cortical areas projecting (in a lower density) to the VMP were the motor cortex, the cortex along the anterior ectosylvian sulcus, the granular insular cortex, the posterior agranular insular area, the prelimbic area, and the cortex along the posterior rhinal sulcus (SRP). Among other subcortical prosencephalic structures projecting to the VMP are the dorsal claustrum, substantia innominata, hypothalamic formations, and the zona incerta. Projections originated from the brainstem in the lateral part of the intermediate and deep layers of the superior colliculus, the central gray matter, the locus coeruleus, and the reticular formation. The nucleus tegmenti pedunculopontinus pars compacta, parabrachial nuclei, the vestibular complex, and the spinal trigeminal nucleus were also origins of projections to the VMP. We conclude by emphasizing the important bilateral cortical modulation of the different functions attributed to the VMP: recruiting-response mediation, reticular-activating system participation, and extrapyramidal motor integration. In light of the connections just described, the VMP may be considered as a point for impulses coming from complex association cortical areas and limbic formations to converge with those emanating from cortical and subcortical motor structures.

The cingulate bridge between allocortex, isocortex and thalamus.

The Fink-Heimer silver impregnation and the autoradiographic methods were used to study the fiber projections of the cingulate cortex in the squirrel monkey. It was found that this cortex provides inputs to the straitum, thalamus and several areas of isocortex. Evidence was found for a number of fiber projections (1) Fibers from the anterior limbic area were traced to the central part of the head of the caudate nucleus, putamen, septum, dorsomedial nucleus of the thalamus, anterior hypothalamus and lateral basal nucleus of the amygdala. (2) Projections from the cingulate area were traced to the lateral part of the head of the caudate nucleus, putamen, and to the centromedian, anterior, lateral dorsal, and lateral ventral thalamic nuclei and to medial nuclei of the base of the pons. (3) There were porjections from the retrosplenial area of the anterior, lateral dorsal, dorsomedial, and posterior thalamic nuclei and lateral nuclei of the pons. These results indicate that most of the cingulate gyrus is an intermediate structure between the thalamus and overlying cortex. The anterior limbic area forms a bridge between the thalamus and other areas of the cingulate gyrus and the frontal cortex. (4) the retrosplenial area and the posterior part of the cingulate area bridge the adjacent visual snesory association cortex and pelvic areas of the snesory motor cortex, respectively. These areas of the cingulate gyrus project directly to the striatum as well as to the thalamus, structurally providing limbic system input to subcortical motor structures.