Role Of Subcortical Structures Research Articles

The role of dorsolateral striatum in the effects of deep cerebellar stimulation-mediated motor recovery following ischemic stroke in rodents

Despite great advances in acute care and rehabilitation, stroke remains the leading cause of motor impairment in the industrialized world. We have developed a deep brain stimulation (DBS)-based approach for post-stroke rehabilitation that has shown reproducible effects in rodent models and has been recently translated to humans. Mechanisms underlying the rehabilitative effects of this novel therapy have been largely focused on the ipsilesional cortex, including cortical reorganization, synaptogenesis, neurogenesis and greater expression of markers of long-term potentiation. The role of subcortical structures on its therapeutic benefits, particularly the striatum, remain unclear. In this study, we compared the motor rehabilitative effects of deep cerebellar stimulation in two rodent models of cerebral ischemia: a) cortical ischemia; and b) combined striatal and cortical ischemia. All animals underwent the same procedures, including implantation of the electrodes and tethered connections for stimulation. Both experimental groups received four weeks of continuous lateral cerebellar nucleus (LCN) DBS and each was paired with a no stimulation, sham, group. Fine motor function was indexed using the pasta matrix task. Brain tissue was harvested for histology and immunohistochemical analyses. In the cortical-only ischemia, the average pasta matrix performance of both sham and stimulated groups reduced from 19 to 24 pieces to 7—8 pieces following the stroke induction. At the end of the four-week treatment, the performance of stimulated group was significantly greater than that of sham group (14 pieces vs 7 pieces, p < 0.0001). Similarly, in the combined cortical and striatal ischemia, the performance of both sham and stimulated groups reduced from 29 to 30 pieces to 7–11 pieces following the stroke induction. However, at the end of the four-week treatment, the performance of stimulated group was not significantly greater than that of sham group (15 pieces vs 11 pieces, p = 0.452). In the post-mortem analysis, the number of cells expressing CaMKIIα at the perilesional cortical and striatum of the LCN DBS treated animals receiving cortical-only stroke elevated but not those receiving cortical+striatal stroke. The current findings suggested that the observed, LCN DBS-enhanced motor recovery and perilesional plasticity may involve striatal mechanisms.

Нейропсихологические и нейробиологические основы восстановления высших корковых функций. Модулярная теория VS теория системной и динамической локализации функций

Background. Neuropsychology and neuroscience solve a number of general issues concerning the relationship between brain and psyche, the principles of the structural and functional brain organization, the cerebral basis of mental processes, patterns of damage and recovery of complex behavioral systems. Neuroscientific basis for higher brain function recovery allows us to explain the regularities of neuroplasticity. The neuropsychological basis makes it possible to build an adequate programme of neuropsychological rehabilitation, taking into account not only psychological but also biological patterns. Thus, it is necessary to strengthen the integration of neuroscientific and neuropsychological points of views in this domain. Objective. The study aims to analyse the strengths and weaknesses of modular theory and the theory of system and dynamic localization of functions in solving the question of structural and functional brain organization and their reflection in approaches to neuropsychological rehabilitation. Methods. Comparative analysis and the method of generalization were applied. Results. Modular theory and the theory of system and dynamic localization of functions have a number of common key points. 1. The principle of the system (distributed) organization of higher cortical functions. 2. Horizontal-vertical structure of higher brain functions. 3. Сortical function is the constellation of factors/modules. 4 Functional unit (factor/module) is a structural element of different brain systems. 5. Damage of a functional unit leads to a selective damage of a certain group of cognitive processes. Theories differ in understanding the content of a functional unit of a brain, which leads to differing understandings of the typology in the ways to recovery. The study considers the role of subcortical structures in providing behavioral automatisms. The paper shows the importance of the intact conduction pathways in making rehabilitation prognosis. Conclusion. The study reveals limitations of the concept of factor in explaining the variability and dissociative picture of a neuropsychological symptom. The content of factor as well as its structural elements are to be revised and described. Certain statements of the theory of system and dynamic localization of functions have to be modified in order to reflect the regularities of neuroplasticity in the methodology of neuropsychological rehabilitation.

P01.14.B Visuospatial selective attention deficit after resection of right hemisphere gliomas: a multivariate lesion symptom mapping and diffusion tractography study

Abstract Background The ability to select relevant information to current behavioural goals despite concomitant distractors (i.e. selective attention) is crucial for daily life. Despite the implication of fronto-parietal network in sustaining visuospatial selective attention has been considered crucial, the role of subcortical structures is still unclear. Aim of this study was to evaluate the impact of neurosurgical removal of right gliomas on visuospatial selective attention performances. Material and Methods The visuospatial selective attention domain was assessed pre- and postoperatively (1 month follow-up) in 73 patients operated for right hemisphere gliomas. Support-vector-regression lesion-symptom mapping and disconnectome analysis (Lesion Quantification Toolkit, HCP 1065 data) were used to evaluate the relationship between the resection cavities and the postoperative performance on a standardized selective attention test. To test and refine the atlas-based results, in a subset of 17 patients with preoperative diffusion tractography, the postoperative outcome was correlated with the percentage of disconnection for different white matter tracts. Results Results showed that resection of a cluster enclosing the SMA-complex and the surrounding white matter was significantly associated with a decline in visuospatial selective attention performances (p&amp;lt;.05). Disconnectome analysis at population level revealed that the deficit was significantly correlated with the resection of superior cortico-striatal fibres, superior thalamic radiations, corticopontine projections, callosal connections and fibres of the frontal aslant tract. Within all the cortico-subcortical terminations of these tracts, disconnection of streamlines of the SMA-complex was the most associated with selective attention deficits. Tractography in single patients confirmed the population level results and suggested that ventro-lateral resections in case of inferior frontal or insular tumours significantly disconnecting the frontal aslant tract but sparing superior projection fibres were not associated with any postoperative disturbances. Conclusion Results show converging evidence to support a critical role for the SMA/preSMA and its projections in maintaining efficiency of attentive control. The present results reveal the importance of a fronto-medial descending connectivity in mediating the voluntary control of visuospatial selective attention. From a surgical standpoint, to avoid postoperative deficits, it seems crucial to preserve SMA projection pathways, while the disconnection of the frontal aslant tract is feasible without any postoperative decline.

Differential responses to breath-holding, voluntary deep breathing and hypercapnia in left and right dorsal anterior cingulate.

What is the central question of this study? What is the role of dorsal anterior cingulate cortex (ACC) in respiration control in humans? What is the main finding and its importance? Direct evidence is provided for a role of the ACC in respiratory control in humans. The neurophysiological responses in dorsal ACC to different breathing tasks varied and were different between left and right ACC. The role of subcortical structures and cerebral cortex in the maintenance of respiratory homeostasis in humans remains poorly understood. Emerging evidence suggests an important role of the anterior cingulate cortex (ACC) in respiratory control. In this study, local field potentials (LFPs) from dorsal ACC were recorded in humans through implanted deep brain electrodes during several breathing activities, including voluntary activities of breath-holding and deep breathing, and involuntary activities of inspiration of varying concentrations of carbon dioxide (1%, 3%, 5% and 7%). We found that the breath-holding task induced significant unilateral left-sided ACC changes in LFP power, including an increased activity in lower frequency bands (3-5Hz) and decreased activity in higher frequency bands (12-26Hz). The respiratory task involving reflex increase in ventilation due to hypercapnia (raised inspired CO2 ) was associated with bilateral changes in activity of the ACC (again with increased activity in lower frequency bands and reduced activity in higher frequency bands). The voluntary breathing task with associated hypocapnia (deep breathing) induced bilateral changes in activity within low frequency bands. Furthermore, probabilistic diffusion tractography analysis showed left-sided connection of the ACC with the insula and frontal operculum, and bilateral connections within subsections of the cingulate gyrus and the thalamus. This electrophysiological analysis provides direct evidence for a role of the ACC in respiratory control in humans.

The morphological characteristics of hippocampus and thalamus in mesial temporal lobe epilepsy

BackgroundMesial temporal lobe epilepsy (MTLE) is the most common form of focal epilepsy, which is frequently characterized by hippocampal sclerosis (HS). Accumulating studies have suggested widespread cortico-cortical connections related to MTLE. The role of subcortical structures involved in general epilepsy has been extensively investigated, but it is still limited in MTLE. Our purpose was to determine the specific morphological correlation between sclerotic hippocampal and thalamic sub-regions, using quantitative analysis, in MTLE.MethodsIn this study, 23 MTLE patients with unilateral hippocampal sclerosis and 24 healthy controls were examined with three-dimensional T1 MRI. Volume quantitative analysis in the hippocampus and thalamus was conducted and group-related volumetric difference was assessed. Moreover, vertex analysis was further performed using automated software to delineate detailed morphological patterns of the hippocampus and thalamus. The correlation was used to examine whether there is a relationship between volume changes of two subcortical structures and clinical characteristics.ResultsThe patients had a significant volume decrease in the sclerotic hippocampus (p < 0.001). Compared to controls, obvious atrophic patterns were observed in the bilateral hippocampus in MTLE (p < 0.05). Only small patches of shrinkage were noted in the bilateral thalamus (p < 0.05). Moreover, the volume change of the hippocampus had a significant positive correlation with that of the thalamus (P < 0.001). Intriguingly, volume changes of the hippocampus and thalamus were correlated with the duration of epilepsy (hippocampus: P = 0.024; thalamus: P = 0.022). However, only volume changes of thalamus possibly differentiated between two prognostic groups in patients (P = 0.026).ConclusionsWe demonstrated the morphological characteristics of the hippocampus and thalamus in MTLE, providing new insights into the interrelated mechanisms between the hippocampus and thalamus, which have potential clinical significance for refining neuromodulated targets.

Newer Paradigms in Language Neurobiology.

The field of language research has seen tremendous progress in the last two decades. Advances in neuro-imaging and stimulation mapping have changed the way we conceive the neural basis of speech and language processing. In the past, the Wernicke-Lichtheim model was the most influential model explaining the neuro-anatomical basis of language. More recently, the concept of dual stream language processing has emerged, wherein separate dorsal and ventral networks are synergistically involved in phonological (sound to articulation) and semantic (sound to meaning) processing respectively. In this review article, we highlight new insights and approaches to the neurobiology of language, across different aspects of language processing like perception, comprehension, production, hemisphere lateralization, role of subcortical structures and effect of damage to language networks.

Preserved but Less Efficient Control of Response Interference After Unilateral Lesions of the Striatum.

Previous research on the neural basis of cognitive control processes has mainly focused on cortical areas, while the role of subcortical structures in cognitive control is less clear. Models of basal ganglia function as well as clinical studies in neurodegenerative diseases suggest that the striatum (putamen and caudate nucleus) modulates the inhibition of interfering responses and thereby contributes to an important aspect of cognitive control, namely response interference control. To further investigate the putative role of the striatum in the control of response interference, 23 patients with stroke-induced lesions of the striatum and 32 age-matched neurologically healthy controls performed a unimanual version of the Simon task. In the Simon task, the correspondence between stimulus location and response location is manipulated so that control over response interference can be inferred from the reaction time costs in incongruent trials. Results showed that stroke patients responded overall slower and more erroneous than controls. The difference in response times (RTs) between incongruent and congruent trials (known as the Simon effect) was smaller in the ipsilesional/-lateral hemifield, but did not differ significantly between groups. However, in contrast to controls, stroke patients exhibited an abnormally stable Simon effect across the reaction time distribution indicating a reduced efficiency of the inhibition process. Thus, in stroke patients unilateral lesions of the striatum did not significantly impair the general ability to control response interference, but led to less efficient selective inhibition of interfering responses.

Influence of the epileptogenic zone on epilepsy-related behavioral and psychological dysfunction

Epilepsy may be associated with both ictal (during seizures) and interictal (between seizures) disturbance in psychological state and behavior. Ictal psychobehavioral change is particularly a feature of epileptogenic zones (EZ) involving frontal lobe and mesial temporal lobe structures. In frontal lobe epilepsy, a clear rostrocaudal anatomical-functional gradient has been demonstrated with regards to ictal behavioral expression, using stereoelectroencephalography (SEEG) [1] . The role of subcortical structures in ictal behavioral production is probably crucial, and can be surmised to be closely linked to cortical epileptic activity, but specific patterns of cortico-subcortical organization in epilepsy remain unclear. Parallels have been drawn between certain behavior patterns observable in seizures and in other neurological conditions, notably sleep disorders [2] . The stereotyped nature of intra-subject ictal behavioral expression evokes a “learning” process subserved by cortico-basal ganglia circuits. Ictal and interictal psychobehavioral dysfunction may co-exist or not. Involvement of the paralimbic system in the EZ is more often associated with seizures involving emotional expression, whether subjective or objective, and may be more often associated with interictal psychiatric and behavioral disturbance. A gradient from “internal” (subjective) to “external” (objective) expression of this may be seen within limbic system structures depending on main structures involved. Animal models of emotion [3] may offer an interesting framework for thinking about neural substrates of ictal and interictal psychobehavioral change in epilepsy, particularly in terms of investigating cortico-subcortical connections.

Role of subcortical structures on cognitive and social function in schizophrenia

Subcortical regions have a pivotal role in cognitive, affective, and social functions in humans, and the structural and functional abnormalities of the regions have been associated with various psychiatric disorders. Although previous studies focused on the neurocognitive and socio-functional consequences of prefrontal and tempolo-limbic abnormalities in psychiatric disorders, those of subcortical structures remain largely unknown. Recently, MRI volume alterations in subcortical structures in patients with schizophrenia have been replicated in large-scale meta-analytic studies. Here we investigated the relationship between volumes of subcortical structures and neurocognitive and socio-functional indices in a large sample of patients with schizophrenia. First, we replicated the results of meta-analyses: the regional volumes of the bilateral hippocampus, amygdala, thalamus and nucleus accumbens were significantly smaller for patients (N = 163) than for healthy controls (HCs, N = 620). Second, in the patient group, the right nucleus accumbens volume was significantly correlated with the Digit Symbol Coding score, which is known as a distinctively characteristic index of cognitive deficits in schizophrenia. Furthermore, the right thalamic volume was significantly correlated with social function scores. In HCs, no significant correlation was found. The results from this large-scale investigation shed light upon the role of specific subcortical nuclei on cognitive and social functioning in schizophrenia.

P 147 Preserved control of response interference after unilateral lesions of the striatum

Background/Objective Previous research on the neural basis of cognitive control processes has mainly focused on cortical areas, while the role of subcortical structures in cognitive control is less clear. Models of basal ganglia function as well as clinical studies in neurodegenerative diseases suggest that the striatum (putamen and nucleus caudatus) modulates the inhibition of response impulses and thereby contributes to an important aspect of cognitive control. The present study aimed at further investigating the putative role of the striatum within the fronto-striatal network in cognitive control processes. Methods Twenty-three patients with unilateral lesions (caused by stroke) involving the striatum and 32 age-matched neurologically healthy controls performed a unimanual version of the Simon task. In the Simon task, the correspondence between stimulus location and response location is manipulated, so that the efficacy of cognitive control processes can be inferred by the (prolonged) reaction times in situations when a response conflict has to be resolved. Results Stroke patients responded overall slower and more erroneous than controls. The difference in response times to incongruent versus congruent trials (known as the Simon effect) was reduced in the ipsilesional/-lateral hemifield, but did not differ significantly between groups in the current unimanual version of the Simon task. Discussion Thus, in stroke patients unilateral lesions of the striatum did not significantly impair cognitive control processes (here: control of response interference). Possible compensatory mechanisms and implications of these findings for theoretical accounts of the Simon effect are discussed.

S85 The modulatory role of subcortical structures on cortical cognitive functions

A direct way of studying the function of the subcortical nuclei is neurophysiological recording of event related electrical activities, i.e. the evoked potentials and oscillations, via the intracranial deep brain electrodes. Based on our own electrophysiological recordings and results of other groups we suggest that the subcortical nuclei are involved in the processing of higher cortical functions. We recorded cognitive tasks-related activities in putamen, pallidum, caudate, ncl. subthalamicus, anterior and posterolateral thalamus. Recordings were performed via intracerebral electrodes (SEEG) or deep brain stimulation (DBS) electrodes in patients with pharmacoresistant epilepsy from basal ganglia ( putamen, pallidum, caudate) and anterior nuclei of thalamus; in patients with Parkinson’s disease and dystonia from the subthalamic nucleus and internal pallidum; posterolateral thalamus was implanted for the treatment of pain. The cognitive role of the subcortical structures was tested in various protocols exploring the cognitive involvement in the motor control, executive functions, attention and orientation, complex visuo-motor tasks, memory encoding and retrieval. A general hypothesis explaining the role of the subcortical structures and the cortico-subcortical interactions in processing cognitive activities is still missing. We suggest that there is a plastic functional network of cortical and subcortical structures that are simultaneously active, with all the time changing mutual interconnections of active and inactive zones in a task related manner. 1. Basal ganglia – thalamocortical loop act as an modulator which may be involved in tuning the widespread cortical functions. An integrative role of the basal ganglia with subsequent modulation of cortical cognitive processing is suggested. 2. Thalamic specific nuclei may modulate specific cognitive functions probably via contextual modulation of certain cortical areas. Subcortical structures, in particular basal ganglia, should be seriously considered as a potential target for neuromodulatory treatment of diseases with cognitive disturbances.

Subcortical shape analysis of progressive mild cognitive impairment in Parkinson's disease.

Cortical neural correlates of ongoing cognitive decline in Parkinson's disease (PD) have been suggested; however, the role of subcortical structures in longitudinal change of cognitive dysfunction in PD has not been fully investigated. Here, we used automatic analysis to explore subcortical brain structures in patients with PD with mild cognitive impairment that converts into PD with dementia. One hundred eighty-two patients with PD with mild cognitive impairment were classified as PD with mild cognitive impairment converters (n = 74) or nonconverters (n = 108), depending on whether they were subsequently diagnosed with dementia in PD. We used surface-based analysis to compare atrophic changes of subcortical brain structures between PD with mild cognitive impairment converters and nonconverters. PD with mild cognitive impairment converters had lower cognitive composite scores in the attention and frontal executive domains than did nonconverters. Subcortical shape analysis revealed that PD with mild cognitive impairment converters had smaller local shape volumes than did nonconverters in the bilateral thalamus, right caudate, and right hippocampus. Logistic regression analysis showed that local shape volumes in the bilateral thalamus and right caudate were significant independent predictors of PD with mild cognitive impairment converters. In the PD with mild cognitive impairment converter group, thalamic local shape volume was associated with semantic fluency and attentional composite score. The present data suggest that the local shape volumes of deep subcortical structures, especially in the caudate and thalamus, may serve as important predictors of the development of dementia in patients with PD. © 2017 International Parkinson and Movement Disorder Society.

Progression of subcortical atrophy in mild Parkinson's disease and its impact on cognition.

Mild cognitive impairment (MCI) is associated with pronounced grey matter atrophy in various brain regions. However, the association between atrophy patterns and progression from no cognitive impairment (NCI) to Parkinson's disease (PD)-MCI is not clearly known. We investigated the pattern and progression of atrophy in subcortical structures and its impact on cognition in patients with mild PD. Sixty-five patients with mild PD with baseline and longitudinal clinical and neuropsychological assessments, and structural magnetic resonance imaging scans were studied. Movement Disorder Society Task Force criteria were used to classify patients with PD into PD-NCI (n = 54) and PD-MCI (n = 11). Based on progression over time, those who remained without cognitive impairment were classified as PD-stable (n = 42) and those who converted to MCI over 18 months were classified as PD-converters (n = 12). FreeSurfer was used to measure cortical thickness and subcortical volumes at baseline and follow-up. Parkinson's disease-MCI showed baseline thalamus atrophy and progressive atrophy in the thalamus, caudate, presubiculum, cornu ammonis 1 and 2-3, and significant memory and executive dysfunction compared with PD-NCI. PD-converters had greater accumbens atrophy at baseline and progressive atrophy in the thalamus, caudate and accumbens with dysfunctions in memory and executive domains. Progression of cognitive impairment in non-demented PD is associated with a specific pattern of subcortical atrophy. Findings from this study will allow future studies to investigate in the role of subcortical structures as a biomarker for PD dementia.

22. Plasticity of sensorimotor system induced by sustained pressure stimulation

Introduction The aim of this study was to assess functional changes occurring at central nervous system (CNS) in healthy volunteers after sustained pressure stimulation according to Vojta (Bauer et al., 1992), a physiotherapeutic method involving induction of a complex motor response, so called reflex locomotion. Although the therapy has been widely used in clinical practice, its underlying neurobiological basis remains a speculation. We hypothesize that the stimulation-driven response induces CNS plasticity at subcortical level detectable by functional magnetic resonance imaging (fMRI), possibly involving specific changes in task-related sensorimotor system activation as well as modulation of resting state networks. Methods Two groups of healthy volunteers were included (17 females and 5 males in each group, mean age 24.5 and 24.7 respectively): Group A receiving stimulation at the Vojta right heel zone and Group B receiving control stimulation of the right ankle. All subjects underwent a single fMRI session using a 1.5T Siemens scanner, including 6 experimental runs employing 3 different conditions: rest (6min); dominant hand finger tapping alternating with rest (6min); intermittent pressure stimulation applied by an experienced therapist (10min). Both rest and finger tapping conditions were tested before and after two consecutive stimulation runs. Statistical analysis, including standard pre-processing, nuisance signal regression and group post hoc contrasts, was carried out using FEAT, and MELODIC followed by Dual Regression, parts of FSL (Jenkinson et al., 2012) 5.0. The resulting statistical maps were thresholded at corrected significance level p Results In finger tapping task, diffuse activation decrease within sensorimotor system was observed in both groups. However, there was significant activation increase mainly in motor nuclei of left thalamus detected only in group A. Additionally, group A showed significant decrease of functional connectivity in the left superior parietal lobule within the bilateral sensorimotor resting-state network. Conclusions Our findings provide evidence that stimulation according to Vojta is associated with specific and persistent changes of brain activation, as compared to the control stimulation. The observed changes could represent neurophysiological correlate of Vojta therapy and suggest an important role of subcortical structures. Acknowledgement Supported by grant GACR 14–22572S.

Differential impact of thalamic versus subthalamic deep brain stimulation on lexical processing

Roles of subcortical structures in language processing are vague, but, interestingly, basal ganglia and thalamic Deep Brain Stimulation can go along with reduced lexical capacities. To deepen the understanding of this impact, we assessed word processing as a function of thalamic versus subthalamic Deep Brain Stimulation.Ten essential tremor patients treated with thalamic and 14 Parkinson׳s disease patients with subthalamic Deep Brain Stimulation performed an acoustic Lexical Decision Task ON and OFF stimulation. Combined analysis of task performance and event-related potentials allowed the determination of processing speed, priming effects, and N400 as neurophysiological correlate of lexical stimulus processing. 12 age-matched healthy participants acted as control subjects.Thalamic Deep Brain Stimulation prolonged word decisions and reduced N400 potentials. No comparable ON–OFF effects were present in patients with subthalamic Deep Brain Stimulation. In the latter group of patients with Parkinson’ disease, N400 amplitudes were, however, abnormally low, whether under active or inactive Deep Brain Stimulation.In conclusion, performance speed and N400 appear to be influenced by state functions, modulated by thalamic, but not subthalamic Deep Brain Stimulation, compatible with concepts of thalamo-cortical engagement in word processing. Clinically, these findings specify cognitive sequels of Deep Brain Stimulation in a target-specific way.

Cortical involvement in focal epilepsies with epileptic spasms

The pathophysiological mechanisms of epileptic spasms are still poorly understood. The role of subcortical structures has been suggested on the basis of non-localized EEG features and from experimental data. The description of asymmetric spasms associated with lateralized EEG patterns has challenged this view and raises the possibility of a cortical origin. This study investigated the cortical organization of partial seizures associated with epileptic spasms in children undergoing intracerebral EEG recordings for presurgical evaluation. Eleven children with drug resistant epileptic spasms and for whom depth electrode recordings were performed were retrospectively studied. In all children several features suggested a focal origin. Cortical involvement was studied using the "Epileptogenicity Index" (EI). A focal origin was finally demonstrated in 10/11 patients. Seven patients demonstrated pre-ictal changes in the seizure onset zone area. EI analysis showed maximal values in the temporal (n=5), parietal (n=1) or frontal (n=5) cortices. EEG changes were also observed in the premotor cortex during spasms in patients with frontal or parietal seizures and in 3/5 patients with temporal lobe seizures. Good surgical outcome (class I or II) was obtained in 7/10 patients. Seizures associated with epileptic spasms may originate from various cortical regions. Premotor/motor cortices are probably involved in determining ictal clinical changes.

44. The cerebellum, basal ganglia and motor timing in movement disorders. Behavioral and fMRI study

Introduction Published studies demonstrated that the cerebellum and basal ganglia participate in various motor and non-motor task related to prediction. In a series of behavioural and functional imaging studies we studied different populations of patients with movements disorders to clarify the role of the cerebellum and basal ganglia with respect to the motor timing. Methods Specifically, we investigated four different groups: (i) patients with early Parkinson’s disease (PD); (ii) patients with sporadic spinocerebellar ataxia (SCA); (iii) patients with essential tremor (ET); (IV) patients with focal dystonia – cervical dystonia (CD) and (v) matched healthy controls. We used a predictive motor timing task that involved mediated interception of a moving target, and we assessed the effect of movement type (acceleration, deceleration, constant), speed (slow, medium, fast), and angle (0°, 15°, 30°) on performance (hit, early error, late error). Using functional magnetic resonance imaging (fMRI) we evaluated the effect of hits, early errors, late errors – and their contrasts. Results Behavioral: The main results showed that the PD group did not significantly differ from the control group. However, the SCA, ET and CD subjects (severe and mild cerebellar damage, respectively) were significantly worse at interception than the other two groups. We found that the PD patients failed to postpone their action until the right moment and to adapt from one trial to the next more often than the controls. Imaging The lobule VI of the right cerebellum was more activated in the healthy controls relative to the PD patients during successful trials. Also, successful trial-by-trial adjustments were associated with more pronounced activation in the right putamen and lobule VI for the healthy controls relative to the PD patients. PD subjects and healthy controls used identical functional circuits to maintain the successful outcome in predictive motor timing behavior, however the strength of effective connectivity differed between these two groups. Conclusions The cerebellum plays an essential role in integrating incoming visual information with motor output when making predictions about upcoming actions. Both the cerebellum and the basal ganglia are necessary for the predictive motor timing in general, with the cerebellum being associated with the postponement of the action until the right moment, and with both the cerebellum and the basal ganglia needed for successful adaptation in the task from one trial to the next. Future studies of the exact roles of subcortical structures in movement disorders is the challenge for the researchers. This work was supported by the project “CEITEC – Central European Institute of Technology” (CZ.1.05/1.1.00/02.0068) from the European Regional Development Fund and by a research project of the Czech Ministry of Health Foundation (2010–2015) NT/13437.

The Role of Fronto-Parietal and Fronto-Striatal Networks in the Development of Working Memory: A Longitudinal Study

The increase in working memory (WM) capacity is an important part of cognitive development during childhood and adolescence. Cross-sectional analyses have associated this development with higher activity, thinner cortex, and white matter maturation in fronto-parietal networks. However, there is still a lack of longitudinal data showing the dynamics of this development and the role of subcortical structures. We included 89 individuals, aged 6-25 years, who were scanned 1-3 times at 2-year intervals. Functional magnetic resonance imaging (fMRI) was used to identify activated areas in superior frontal, intraparietal cortices, and caudate nucleus during performance on a visuo-spatial WM task. Probabilistic tractography determined the anatomical pathways between these regions. In the cross-sectional analysis, WM capacity correlated with activity in frontal and parietal regions, cortical thickness in parietal cortex, and white matter structure [both fractional anisotropy (FA) and white matter volume] of fronto-parietal and fronto-striatal tracts. However, in the longitudinal analysis, FA in white matter tracts and activity in caudate predicted future WM capacity. The results show a dynamic of neural networks underlying WM development in which cortical activity and structure relate to current capacity, while white matter tracts and caudate activity predict future WM capacity.

The Importance of Thalamic Connections: Cognition, Arousal, and Behavior in Thalamic Stroke

Back to table of contents Previous article Next article LettersFull AccessThe Importance of Thalamic Connections: Cognition, Arousal, and Behavior in Thalamic StrokeAnil Srivastava, M.D., David McNeill, M.D., and Rosa Ip, Ph.D.Anil SrivastavaSearch for more papers by this author, M.D., David McNeillSearch for more papers by this author, M.D., and Rosa IpSearch for more papers by this author, Ph.D.Published Online:1 Jul 2013https://doi.org/10.1176/appi.neuropsych.12080206AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The thalamus is a midline, paired, brain structure broadly composed of anterior, medial, and lateral nuclei.1 Appreciation of thalamic connections is important for the clinician presented with thalamic injury. We explore manifestations of thalamic stroke in a man admitted to a neuropsychiatric unit for aggression. Functional anatomy as it pertains to cognition, arousal, and behavior is explored and management is discussed.The patient is a man in his 40s, with community college education and no medical history, who developed vasculitis of unknown etiology involving the thalamoperforating vessels. Infarction largely involved the right thalamus (Figure 1).FIGURE 1. Right Thalamic Infarction: MRI Brain, T2-Weighted Axial Image Without ContrastPhysical aggression was of new onset. The anterior nucleus is the principal relay nucleus for the limbic system, thought to play a role in emotion; it receives the mammilothalamic tract, which, in turn, projects to the cingulate gyrus.2 The dorsomedial nucleus (DM) similarly retains interconnections with the prefrontal cortex, which helps regulate affect and planning. Inputs to the DM include not only the prefrontal cortex but also elements of the limbic system, e.g., the amygdala. Successful treatment of aggression included divalproex sodium 1,000 mg p.o. od, citalopram 20 mg p.o. od, and olanzapine 5 mg p.o. od.Previously unrecognized periods of diminished arousal were observed. These seemed to be of two types: In one, preceding verbal automatisms with focal motor activity were present. Despite a normal waking EEG, consideration to partial complex seizures was given. Seizures secondary to subcortical involvement have been reported,3 and the thalamus, including the reticular nucleus2 and the anterior nucleus,4 may play a role. Gabapentin was initiated at 300 mg p.o. tid, adjunctive to valproic acid. Residual periods of prolonged somnolence, often of quick onset, remained. Ascending projections from the reticular formation, which collects information from multiple sensory modalities, terminate in the thalamus, especially the intralaminar nuclei, and are involved in arousal.1 Modafinil 100 mg p.o. bid was started. A sleep study was conducted and detection of significant central apnea prompted use of continuous positive airway pressure (CPAP). Significantly greater alertness resulted with the above measures.Cognitive changes were noted post-stroke. In particular, neuropsychological deficits were obvious in delayed memory (Repeatable Battery for the Assessment of Neuropsychological Status [RBANS] subtests List Learning and Story Memory), executive functioning (Stroop Color Word Test, Trails B), and visuospatial ability (RBANS subtest Figure Copy). Visuospatial deficits may be especially prominent in right-sided thalamic lesions,2 such as with this patient. The anterior nucleus of the thalamus maintains direct and indirect connections with the hippocampus, thought to subserve memory. Executive function is mediated in part by prefrontal cortex, as above, connected with the dorsomedial nucleus. Interestingly, although not explored in this case, there is a report of improvement in executive functioning in thalamic infarction with the use of donepezil.5Damage to thalamic circuits results in wide-ranging effects, including arousal, cognition, and behavior. Knowledge of functional anatomy is important in the recognition and understanding of such impairment. Successful management may involve use of antiepileptics, antidepressants, antipsychotics, continuous positive airway pressure (CPAP), and stimulants.Ontario Shores Centre for Mental Health Sciences Whitby, Ontario, CanadaCorrespondence: Dr. Anil Srivastava; e-mail: [email protected]comReferences1 Nolte J: The Human Brain: An Introduction to Its Functional Anatomy, 4th Edition. Maryland Hgts., MO, Mosby, 1999Google Scholar2 Schmahmann JD: Vascular syndromes of the thalamus. Stroke 2003; 34:2264–2278Crossref, Medline, Google Scholar3 Norden AD, Blumenfeld H: The role of subcortical structures in human epilepsy. Epilepsy Behav 2002; 3:219–231Crossref, Medline, Google Scholar4 Fisher R, Salanova V, Witt T, et al.: SANTE Study Group: Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia 2010; 51:899–908Crossref, Medline, Google Scholar5 Riveros R, Chabriat H, Flores R, et al.. Effects of donepezil on behavioral manifestations of thalamic infarction: a single-case observation. Front Neurol 2:16Medline, Google Scholar FiguresReferencesCited byDetailsCited ByNone Volume 25Issue 3 Summer 2013Pages E63-E64 Metrics PDF download History Published online 1 July 2013 Published in print 1 July 2013

The role of subcortical structures in recited speech: Studies in Parkinson's disease

The role of subcortical structures in language function is complex and dependent on language task, with studies increasingly showing subcortical involvement for the production of formulaic language, including recited speech. Individuals with Parkinson's disease (PD), with (n = 6) and without (n = 7) surgical treatment, deep brain stimulation (DBS), were compared to healthy adults (n = 14) to determine whether individuals with subcortical dysfunction produce more errors during a recitation speech task. Participants were asked to recite poems, prayers, and rhymes familiar to them in order to determine the effects of subcortical disease on recited speech ability. When compared with healthy controls, the DBS-OFF group produced significantly more error words, suggesting that deficits in recitation arise with severe states of subcortical dysfunction. Individuals with DBS in the ON or OFF conditions did not differ significantly during the recited speech task. Results support a model of language where large units of overlearned language are at least partially modulated by subcortical structures.