Basal Ganglia-thalamocortical Loops Research Articles

Microstructural white matter changes underlying speech deficits in Parkinson’s disease

Speech impairments are one of the common symptoms of individuals with Parkinson’s disease (PD). However, little is known about the underlying neuroanatomical structural deficits specifically in the basal ganglia-thalamocortical (BGTC) loop in the speech deficits of PD. Here we investigated white matter differences in PD using probabilistic tractography. Diffusion tensor imaging data were downloaded from the Parkinson’s Progression Markers Initiative database. We included three groups of participants: 20 PD individuals with speech deficits, 20 PD individuals without speech deficits, and 20 age- and gender-matched control participants. Overall, PD individuals with speech deficits had higher mean diffusivity in the BGTC pathway in the left hemisphere compared with PD individuals without speech deficits. The present study exhibits that there may be a distinct pathophysiological profile of white matter for speech deficits in PD.

White matter microstructural differences underlying beta oscillations during speech in adults who stutter

The basal ganglia-thalamocortical (BGTC) loop may underlie speech deficits in developmental stuttering. In this study, we investigated the relationship between abnormal cortical neural oscillations and structural integrity alterations in adults who stutter (AWS) using a novel magnetoencephalography (MEG) guided tractography approach. Beta oscillations were analyzed using sensorimotor speech MEG, and white matter pathways were examined using tract-based spatial statistics (TBSS) and probabilistic tractography in 11 AWS and 11 fluent speakers. TBSS analysis revealed overlap between cortical regions of increased beta suppression localized to the mouth motor area and a reduced fractional anisotropy (FA) in the AWS group. MEG-guided tractography showed reduced FA within the BGTC loop from left putamen to subject-specific MEG peak. This is the first study to provide evidence that structural abnormalities may be associated with functional deficits in stuttering and reflect a network deficit within the BGTC loop that includes areas of the left ventral premotor cortex and putamen.

Disrupted basal ganglia-thalamocortical loops in focal to bilateral tonic-clonic seizures.

Focal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, and unfavourable treatment outcomes. Achieving greater understanding of their underlying circuitry offers better opportunity to control these seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia-thalamus network with resting state functional MRI in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for >1 year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus-mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of 'disconnection' simulations, we showed that these changes in interactive profiles of the basal ganglia-thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum-modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.

Hyperactivity of Basal Ganglia in Patients With Parkinson's Disease During Internally Guided Voluntary Movements.

The contribution of different brain areas to internally guided (IG) and externally triggered (ET) movements has been a topic of debate. It has been hypothesized that IG movements are performed mainly through the basal ganglia-thalamocortical loop while ET movements are through the cerebello-thalamocortical pathway. We hypothesized that basal ganglia activity would be modified in patients with Parkinson's disease during IG movement as compared with normal subjects. We used functional MRI (fMRI) to investigate the differences between IG and ET motor tasks. Twenty healthy participants and 20 Parkinson's disease patients (OFF-state) were asked to perform hand movements in response to sound stimuli (ET) and in advance of the stimuli (IG). We showed that ET movements evoked activation of a few large clusters in the contralateral motor areas: the sensorimotor and premotor cortex, supplementary motor area (SMA), insula, putamen, motor thalamus and ipsilateral cerebellum. IG movements additionally evoked activation of a large number of small clusters distributed in different brain areas including the parietal and frontal lobes. Comparison between the activity of Parkinson's disease patients and healthy volunteers showed few important differences. We observed that along with the activity of the posterior areas, an activation of the anterior areas of putamen was observed during IG movements. We also found hyperactivity of the ventral thalamus for both movements. These results showed that IG movements in PD patients were made with the involvement of both sensorimotor and associative basal ganglia-thalamocortical loops.

Subthalamic Nucleus Neurons Differentially Encode Early and Late Aspects of Speech Production.

Basal ganglia-thalamocortical loops mediate all motor behavior, yet little detail is known about the role of basal ganglia nuclei in speech production. Using intracranial recording during deep brain stimulation surgery in humans with Parkinson's disease, we tested the hypothesis that the firing rate of subthalamic nucleus neurons is modulated in sync with motor execution aspects of speech. Nearly half of 79 unit recordings exhibited firing-rate modulation during a syllable reading task across 12 subjects (male and female). Trial-to-trial timing of changes in subthalamic neuronal activity, relative to cue onset versus production onset, revealed that locking to cue presentation was associated more with units that decreased firing rate, whereas locking to speech onset was associated more with units that increased firing rate. These unique data indicate that subthalamic activity is dynamic during the production of speech, reflecting temporally-dependent inhibition and excitation of separate populations of subthalamic neurons.SIGNIFICANCE STATEMENT The basal ganglia are widely assumed to participate in speech production, yet no prior studies have reported detailed examination of speech-related activity in basal ganglia nuclei. Using microelectrode recordings from the subthalamic nucleus during a single-syllable reading task, in awake humans undergoing deep brain stimulation implantation surgery, we show that the firing rate of subthalamic nucleus neurons is modulated in response to motor execution aspects of speech. These results are the first to establish a role for subthalamic nucleus neurons in encoding of aspects of speech production, and they lay the groundwork for launching a modern subfield to explore basal ganglia function in human speech.

Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement.

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate.NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also demonstrate, for the first time in humans, a mechanism through which the premotor and sensory cortices are functionally connected to the STN.

The influence of acetylcholine, dopamine, and GABA on the functioning of the corticostriatal neuronal network in Alzheimer’s and Parkinson’s diseases: A hypothetical mechanism

A proposed model of the functioning of the basal ganglia complements the existing opinions about the complex interaction between cholinergic and dopaminergic systems. A hypothesis is proposed that one of the means of interaction between these systems is the operation of a negative feedback loop. In this loop, a conditioned stimulus evokes the excitation of dopaminergic neurons and GABAergic cells with long axons in the dopaminergic nuclei, which leads to an increase in the influence on dopamine D2 receptors on striatal cholinergic interneurons; an increase in their inhibition can lead to a pause in their responses. In turn, during this pause reduced action on presynaptic nicotinic receptors at axon terminals of dopaminergic neurons results in a decrease in dopamine release. In addition, dopaminergic neurons are under the inhibitory action of GABAergic striatonigral cells in the striosomes of the dorsal striatum and clusters in the ventral striatum. During the pause, stimulation of M2/M4 receptors located on these striatonigral cells weakens, which should promote potentiation of their excitation, subsequent enhancement of the inhibition of dopaminergic cells, and a decrease in the dopamine concentration in the striatum. In addition, a decrease in the stimulation of M1 receptors on striatopallidal cells and M2 receptors on striatonigral cells of the matrix during the pause should promote synergistic disinhibition through the direct and indirect pathways via the basal ganglia of certain groups of thalamic neurons and enhancement of the excitation of neocortical neurons connected with them. This interaction between cholinergic and dopaminergic systems contributes to the normal functioning of the various parallel cortico–basal ganglia–thalamocortical loops, which play a determining role in movement choice, sensory perception, learning, and intentional behavior. The proposed model implies that cholinergic and dopaminergic denervation of different structures, as well as changes in the density and affinity of receptors that are sensitive to acetylcholine, dopamine, and NMDA, which are typical for Alzheimer’s and Parkinson’s diseases, should lead to abnormal functioning of these loops. This may underlie various cognitive and motor disorders.

EP 68. Identification of electrophysiological biomarkers in a novel animal model of Tourette Syndrome

Introduction Treating Tourette syndrome (TS) remains challenging as therapies fail to take temporal presentation of symptoms into account. Therefore, to optimize therapies the investigation of biomarkers predicting repetitive behavior is required. Objectives We are currently studying repetitive behavior and associated electrophysiological changes in a new animal model of Tourette syndrome – the dopamine transporter (DAT) over-expressing rat model. The DAT rat resembles TS pathology in various aspects, including marked up-regulation of D2/D1 receptors, brain site-specific dopamine alterations and decrease in parvalbumin expressing interneurons in the caudate putamen. In line with clinical findings, the DAT rats display time-locked increase in tic-like behavior following amphetamine application. Math/meth To study stereotypic behavior, extracellular bipolar in vivo recordings were conducted under urethane anesthesia in different areas of the basal-ganglia thalamo-cortical loop for 4 h (2 h before (baseline) and 2 h after amphetamine). Signals were amplified, filtered (0.05–250 Hz) and sampled at 1 kHz. Power Spectral Densities were calculated using Spike 2 software (FFT size 1024/0.0256 s, Hanning Window) for baseline and post amphetamine time-windows, where behavioral analysis revealed stereotypy or not. Power-spectra were normalized to the mean s. d. of power between 103–147 Hz and 153–197 Hz power. Results Results show that DAT rats at the time-point of tic induction, exhibit time-locked abnormalities in alpha and beta bands, especially in the dorsomedial thalamus. This indicates characteristic electrophysiological modulation temporally related to distinct repetitive behavior. Conclusion The time-locked manifestation allows us to further investigate biomarkers of repetitive behavior and to employ this in constructing a close-loop stimulation device treating repetitive behavior in a controlled fashion.

Ventral Medial Thalamic Nucleus Promotes Synchronization of Increased High Beta Oscillatory Activity in the Basal Ganglia-Thalamocortical Network of the Hemiparkinsonian Rat.

Parkinson's disease symptoms are associated with dramatic increases in synchronized beta range (15-35 Hz) oscillatory local field activity in several brain areas involved in motor control, but the mechanisms promoting this activity and its functional significance remain unresolved. This oscillatory activity can be recorded in awake behaving rats with unilateral dopamine cell lesions using chronically implanted electrodes. Although these rats have motor deficits, they can walk on a circular treadmill in the direction ipsilateral to their lesion. This study establishes a critical role for the ventral medial thalamus in the propagation of this exaggerated beta range oscillatory activity and the sequential entrainment of structures throughout the basal ganglia-thalamocortical loop in the lesioned hemisphere of hemiparkinsonian rats during treadmill walking.

Intraoperative electrocorticography for physiological research in movement disorders: principles and experience in 200 cases.

OBJECTIVE Contemporary theories of the pathophysiology of movement disorders emphasize abnormal oscillatory activity in basal ganglia-thalamocortical loops, but these have been studied in humans mainly using depth recordings. Recording from the surface of the cortex using electrocorticography (ECoG) provides a much higher amplitude signal than depth recordings, is less susceptible to deep brain stimulation (DBS) artifacts, and yields a surrogate measure of population spiking via "broadband gamma" (50-200 Hz) activity. Therefore, a technical approach to movement disorders surgery was developed that employs intraoperative ECoG as a research tool. METHODS One hundred eighty-eight patients undergoing DBS for the treatment of movement disorders were studied under an institutional review board-approved protocol. Through the standard bur hole exposure that is clinically indicated for DBS lead insertion, a strip electrode (6 or 28 contacts) was inserted to cover the primary motor or prefrontal cortical areas. Localization was confirmed by the reversal of the somatosensory evoked potential and intraoperative CT or 2D fluoroscopy. The ECoG potentials were recorded at rest and during a variety of tasks and analyzed offline in the frequency domain, focusing on activity between 3 and 200 Hz. Strips were removed prior to closure. Postoperative MRI was inspected for edema, signal change, or hematoma that could be related to the placement of the ECoG strip. RESULTS One hundred ninety-eight (99%) strips were successfully placed. Two ECoG placements were aborted due to resistance during the attempted passage of the electrode. Perioperative surgical complications occurred in 8 patients, including 5 hardware infections, 1 delayed chronic subdural hematoma requiring evacuation, 1 intraparenchymal hematoma, and 1 venous infarction distant from the site of the recording. None of these appeared to be directly related to the use of ECoG. CONCLUSIONS Intraoperative ECoG has long been used in neurosurgery for functional mapping and localization of seizure foci. As applied during DBS surgery, it has become an important research tool for understanding the brain networks in movement disorders and the mechanisms of therapeutic stimulation. In experienced hands, the technique appears to add minimal risk to surgery.

Motor System Interactions in the Beta Band Decrease during Loss of Consciousness.

Communication between brain areas and how they are influenced by changes in consciousness are not fully understood. One hypothesis is that brain areas communicate via oscillatory processes, utilizing network-specific frequency bands, that can be measured with metrics that reflect between-region interactions, such as coherence and phase amplitude coupling (PAC). To evaluate this hypothesis and understand how these interactions are modulated by state changes, we analyzed electrophysiological recordings in humans at different nodes of one well-studied brain network: the basal ganglia-thalamocortical loops of the motor system during loss of consciousness induced by anesthesia. We recorded simultaneous electrocorticography over primary motor cortex (M1) with local field potentials from subcortical motor regions (either basal ganglia or thalamus) in 15 movement disorder patients during anesthesia (propofol) induction as a part of their surgery for deep brain stimulation. We observed reduced coherence and PAC between M1 and the subcortical nuclei, which was specific to the beta band (∼18-24 Hz). The fact that this pattern occurs selectively in beta underscores the importance of this frequency band in the motor system and supports the idea that oscillatory interactions at specific frequencies are related to the capacity for normal brain function and behavior.

Nocebo context modulates long-term habituation to heat pain and influences functional connectivity of the operculum.

In the past, nocebo manipulations have been found to modulate pain perception and influence long-term habituation to pain. Recently, neural correlates accompanying this finding have been identified: habituation over days is mirrored by decreased activity in pain-processing brain areas, whereas nocebo-specific modulation specifically involves the opercular cortex. Focusing on duration and central network characteristics of nocebo information in a longitudinal heat pain paradigm, we investigated 40 healthy participants over a period of 21 consecutive days, whereof sessions on days 1, 8, 14, and 21 were performed during functional magnetic resonance imaging scanning. Negative context information was given to half of the participants, inducing a nocebo manipulation through verbal suggestions. The analysis was focused on brain areas associated with habituation and nocebo effects and identified coupled brain regions using functional connectivity analysis. Decreased pain perception over days was reflected in reduced blood oxygenation level dependent signal in pain-processing areas, such as the insula and somatosensory cortices, whereas increased rostral anterior cingulate cortex activation reflected the central correlate for habituation over time. Habituation was significantly less pronounced in the nocebo group. Consistent with previous results, the nocebo manipulation not only modulated pain perception but also was accompanied by the activation of the operculum over an extended period of time. Importantly, the operculum exhibited changes in coupling during nociceptive input over time, as demonstrated by decreased connectivity with the basal ganglia and pinpoints differences, depending on whether a nocebo context was given. These data suggest that negative verbal suggestions prognosticating increasing pain may prevail by modulating basal ganglia-thalamocortical loops.

Elevated synchrony in Parkinson disease detected with electroencephalography.

Parkinson disease (PD) can be difficult to diagnose and treat. Development of a biomarker for PD would reduce these challenges by providing an objective measure of disease. Emerging theories suggest PD is characterized by excessive synchronization in the beta frequency band (∼20Hz) throughout basal ganglia-thalamocortical loops. Recently we showed with invasive electrocorticography that one robust measure of this synchronization is the coupling of beta phase to broadband gamma amplitude (ie, phase-amplitude coupling [PAC]). Other recent work suggests that high-frequency activity is detectable at the scalp using electroencephalography (EEG). Motivated by these findings, we tested whether beta-gamma PAC over sensorimotor cortex, recorded noninvasively with EEG, differs between PD patients off and on medications, and healthy control subjects. Resting EEG was compared from 15 PD patients and 16 healthy control subjects. PD patients were tested on and off medications on different days, in a counterbalanced order. For each data set we calculated PAC and compared results across groups. PAC was elevated in the patients off medications compared to on medications (p = 0.008) and for patients off medications compared to controls (p = 0.009). Elevated PAC is detectable using scalp EEG in PD patients off medications compared to on medications, and compared to healthy controls. This suggests that EEG PAC may provide a noninvasive biomarker of the parkinsonian state. This biomarker could be used as a control signal for closed-loop control of deep brain stimulation devices, for adjustment of dopaminergic treatment, and also has the potential to aid in diagnosis.

Multiple changes of functional connectivity between sensorimotor areas in focal hand dystonia

BackgroundTask-specific focal hand dystonia impairs the control of arm muscles during fine motor skills such as writing (writer's cramp (WC)). Functional imaging found abnormal task-related activation of sensorimotor areas in...

Slaves to the rhythm: coupling of the subthalamic nucleus–globus pallidus network in Parkinsonian oscillations

Slaves to the rhythm: coupling of the subthalamic nucleus–globus pallidus network in Parkinsonian oscillations

Disrupting neuronal transmission: mechanism of DBS?

Applying high-frequency stimulation (HFS) to deep brain structure, known as deep brain stimulation (DBS), has now been recognized an effective therapeutic option for a wide range of neurological and psychiatric disorders. DBS targeting the basal ganglia thalamo-cortical loop, especially the internal segment of the globus pallidus (GPi), subthalamic nucleus (STN) and thalamus, has been widely employed as a successful surgical therapy for movement disorders, such as Parkinson’s disease, dystonia and tremor. However, the neurophysiological mechanism underling the action of DBS remains unclear and is still under debate: does DBS inhibit or excite local neuronal elements? In this review, we will examine this question and propose the alternative interpretation: DBS dissociates inputs and outputs, resulting in disruption of abnormal signal transmission.

Resting State Functional Connectivity is Associated with Cognitive Dysfunction in Non-Demented People with Parkinson's Disease

Parkinson's disease (PD) can result in cognitive impairment. Executive dysfunction often appears early, followed by more widespread deficits later in the course of the disease. Disruption of parallel basal ganglia thalamo-cortical loops that subserve motor and cognitive function has been described in PD. However, there is emerging evidence that the default mode network, a cortical network that is active at rest with reduced activation during task performance, may also play a role in disease related cognitive decline. To determine the relative contribution of the executive control and default mode networks to parkinsonian executive dysfunction in medicated non-demented patients. We used BOLD fMRI to measure resting state functional connectivity in the executive control and default mode (DM) networks, and examined switching, processing speed, working memory/attention and motor performance in 14 medicated non-demented PD participants and 20 controls. Performance on neuropsychological measures was similar across groups. Functional connectivity was not different across disease conditions in the executive control network. DMN functional connectivity was decreased in the PD group, specifically between posterior cingulate, medial prefrontal, and inferior parietal nodes. Greater DMN functional connectivity was associated with faster processing speed in the PD group. The continuous relationship between DMN disconnection and executive task performance indicates a possible biological contributor to parkinsonian cognitive deficits. The dynamics of executive control network change may be different than that of the DMN, suggesting less sensitivity to early cognitive deficits.

Subthalamic Nucleus Neurons Are Synchronized to Primary Motor Cortex Local Field Potentials in Parkinson's Disease

In Parkinson's disease (PD), striatal dopamine denervation results in a cascade of abnormalities in the single-unit activity of downstream basal ganglia nuclei that include increased firing rate, altered firing patterns, and increased oscillatory activity. However, the effects of these abnormalities on cortical function are poorly understood. Here, in humans undergoing deep brain stimulator implantation surgery, we use the novel technique of subdural electrocorticography in combination with subthalamic nucleus (STN) single-unit recording to study basal ganglia-cortex interactions at the millisecond time scale. We show that in patients with PD, STN spiking is synchronized with primary motor cortex (M1) local field potentials in two distinct patterns: first, STN spikes are phase-synchronized with M1 rhythms in the theta, alpha, or beta (4-30 Hz) bands. Second, STN spikes are synchronized with M1 gamma activity over a broad spectral range (50-200 Hz). The amplitude of STN spike-synchronized gamma activity in M1 is itself rhythmically modulated by the phase of a lower-frequency rhythm (phase-amplitude coupling), such that "waves" of phase-synchronized gamma activity precede the occurrence of STN spikes. We show the disease specificity of these phenomena in PD, by comparison with STN-M1 paired recordings performed in a group of patients with a different disorder, primary craniocervical dystonia. Our findings support a model of the basal ganglia-thalamocortical loop in PD in which gamma activity in primary motor cortex, modulated by the phase of low-frequency rhythms, drives STN unit discharge.

Lateral regions of the rodent striatum reveal elevated glutamate decarboxylase 1 mRNA expression in medium‐sized projection neurons

The GABA-synthesizing enzymes glutamate decarboxylase (GAD)1 and GAD2 are universally contained in GABAergic neurons in the central nervous system of the mouse and rat. The two isoforms are almost identically expressed throughout the brain and spinal cord. By using in situ hybridization, we found that the mouse lateral striatum concentrates medium-sized projection neurons with high-level expression of GAD1, but not of GAD2, mRNA. This was confirmed with several types of riboprobe, including those directed to the 5'-noncoding, 3'-noncoding and coding regions. Immunohistochemical localization of GAD1 also revealed predominant localization of the enzyme in the same striatal region. The lateral region of the mouse striatum, harboring such neurons, is ovoid in shape and extends between interaural +4.8 and +2.8, and at lateral 2.8 and dorsoventral 2.0. This intriguing region corresponds to the area that receives afferent inputs from the primary motor and sensory cortex that are presumably related to mouth and forelimb representations. The lateral striatum is included in the basal ganglia-thalamocortical loop, and is most vulnerable to various noxious stimuli in the neurodegeneration processes involving the basal ganglia. We have confirmed elevated expression of GAD1 mRNA, but not of GAD2 mRNA, also in the rat lateral striatum. Image analysis favored the view that the regional increase is caused by elevated cellular expression, and that the greatest number of medium-sized spiny neurons were positive for GAD1 mRNA. The GAD1 mRNA distribution in the mouse lateral striatum partially resembled those of GPR155 and cannabinoid receptor type 1 mRNAs, suggesting functional cooperation in some neurons.

Abstract 2800: Focal Dorsolateral Basal Ganglia Lesions Impair Identification Of Facial Emotions Signaling Threat

Background: Survival may depend on the ability to efficiently identify threats signaled by the emotional content of facial expressions. While current neural models of facial emotion processing do not prominently feature the basal ganglia, evidence from clinical and functional imagi¬ng studies suggest involvement of the ventral striatum. Methods: To assess the specific role of the basal ganglia in emotion processing, we compared basic facial emotion identification in 23 young patients with a pure focal basal ganglia stroke (mean age 44.9 ± 11.6; 10 males) to 68 matched healthy controls (43.8 years ± 14.0; 27 males). We used quantitative MRI lesion analysis to assess the relationship between basal ganglia location and basic emotion identification. To assess whether facial emotion identification might be related to non-specific lesion effects, we also assessed a wide range of cognitive and motor abilities and screened participants for co-morbid conditions such as depression or anxiety. In addition, we assessed social behavior in terms of social adaptability and the ability to return to work. Results: (1) Basic emotion identification was impaired following focal lesions limited to the basal ganglia. (2) The identification impairment was limited to threat-related emotions, including anger, fear and disgust identification, suggesting a role for the basal ganglia in threat detection. These findings may reflect altered gating mechanisms for facial emotion displays conveying threat signals, with the basal ganglia selecting information relevant to safety. (3) We found that emotion identification impairments adversely affect social behavior, suggesting that emotion identification skills may be of substantial practical importance, and should be considered in the clinical assessment and rehabilitation of patients with basal ganglia lesions. Conclusions: Dorsolateral striatal lesions may affect threat-related emotion identification by disrupting limbic basal ganglia-thalamocortical loop functions associating threat detection with selection of appropriate escape or defensive actions that can preserve individual safety. From a clinical perspective, while the impact of emotion identification impairment on social behavior should be more thoroughly examined in further studies, the consequences of basal ganglia damage appear to be detectible at the individual level. Figure legend: Lesion overlap for patients with identification impairments for anger (red); fear (blue) disgust (green) and all threat emotion (yellow).