Subcortical Mechanisms Research Articles

Neocortical long-range inhibition promotes cortical synchrony and sleep.

Behavioral states such as sleep and wake are highly correlated with specific patterns of rhythmic activity in the cortex. During low arousal states such as slow wave sleep, the cortex is synchronized and dominated by low frequency rhythms coordinated across multiple regions. Although recent evidence suggests that GABAergic inhibitory neurons are key players in cortical state modulation, the in vivo circuit mechanisms coordinating synchronized activity among local and distant neocortical networks are not well understood. Here, we show that somatostatin and chondrolectin co-expressing cells (Sst-Chodl cells), a sparse and unique class of neocortical inhibitory neurons, are selectively active during low arousal states and are largely silent during periods of high arousal. In contrast to other neocortical inhibitory neurons, we show these neurons have long-range axons that project across neocortical areas. Activation of Sst-Chodl cells is sufficient to promote synchronized cortical states characteristic of low arousal, with increased spike co-firing and low frequency brain rhythms, and to alter behavioral states by promoting sleep. Contrary to the prevailing belief that sleep is exclusively driven by subcortical mechanisms, our findings reveal that these long-range inhibitory neurons not only track changes in behavioral state but are sufficient to induce both sleep-like cortical states and sleep behavior, establishing a crucial circuit component in regulating behavioral states.

Cortical and Subcortical Mechanisms of Orthographic Word-form Learning.

We examined the initial stages of orthographic learning in real time as literate adults learned spellings for spoken pseudowords during fMRI scanning. Participants were required to learn and store orthographic word forms because the pseudoword spellings were not uniquely predictable from sound to letter mappings. With eight learning trials per word form, we observed changes in the brain's response as learning was taking place. Accuracy was evaluated during learning, immediately after scanning, and 1 week later. We found evidence of two distinct learning systems-hippocampal and neocortical-operating during orthographic learning, consistent with the predictions of dual systems theories of learning/memory such as the complementary learning systems framework [McClelland, J. L., McNaughton, B. L., & O'Reilly, R. C. Why there are complementary learning systems in the hippocampus and neocortex: Insights from the successes and failures of connectionist models of learning and memory. Psychological Review, 102, 419-457, 1995]. The bilateral hippocampus and the visual word form area (VWFA) showed significant BOLD response changes over learning, with the former exhibiting a rising pattern and the latter exhibiting a falling pattern. Moreover, greater BOLD signal increase in the hippocampus was associated with better postscan recall. In addition, we identified two distinct bilateral brain networks that mirrored the rising and falling patterns of the hippocampus and VWFA. Functional connectivity analysis revealed that regions within each network were internally synchronized. These novel findings highlight, for the first time, the relevance of multiple learning systems in orthographic learning and provide a paradigm that can be used to address critical gaps in our understanding of the neural bases of orthographic learning in general and orthographic word-form learning specifically.

Subcortical neural mechanisms of childhood trauma impacts on personality traits

This study aims to explore the relationships between childhood trauma (CT), personality traits, and subcortical structures. 171 healthy individuals completed the Childhood Trauma Questionnaire (CTQ), the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI), and underwent 3D T1-weighted MRI scans. Linear regression analyses indicated the complex relationship between CT, personality traits, and subcortical gray matter volume (GMV). Mediation analyses revealed that the right hippocampal GMV partially mediated the effects of CT on neuroticism. These findings suggest that CT affects the development of the Big Five personality traits, and alterations in subcortical structures are closely related to this process. Altered GMV in the right hippocampus may be a key neural mechanism for CT-induced neuroticism.

Toe stimulation improves tactile perception of the genitals.

The human body is represented in a topographic pattern in the primary somatosensory cortex (S1), and genital representation is displaced below the toe representation. However, the relationship between the representation of the genitals and toe in S1 remains unclear. In this study, tactile stimulation was applied to the big toe in healthy subjects to observe changes in tactile acuity in the unstimulated genital area, abdomen, and metacarpal dorsal. Then tactile stimulation was applied to the right abdomen and metacarpal dorsal to observe changes in tactile acuity in bilateral genitals. The results revealed that tactile stimulation of the big toe led to a reduction in the 2-point discrimination threshold (2PDT) not only in the stimulated big toe but also in the bilateral unstimulated genitals, whereas the bilateral abdomen and metacarpal dorsal threshold remained unchanged. On the other hand, tactile stimulation of the abdomen and metacarpal dorsal did not elicit 2-point discrimination threshold changes in the bilateral genitals. Cortical and subcortical mechanisms have been proposed to account for the findings. One explanation involves the intracortical interaction between 2 adjacent representations. Another possible explanation is that the information content of a specific body part is broadly distributed across the S1. Moreover, exploring the links between human behaviors and changes in the cerebral cortex is of significant importance.

Perception of visual variance is mediated by subcortical mechanisms

Variance characterizes the structure of the environment. This statistical concept plays a critical role in evaluating the reliability of evidence for human decision-making. The present study examined the involvement of subcortical structures in the processing of visual variance. To this end, we used a stereoscope to sequentially present two circle arrays in a dichoptic or monocular fashion while participants compared the perceived variance of the two arrays. In Experiment 1, two arrays were presented monocularly to the same eye, dichopticly to different eyes, or binocularly to both eyes. The variance judgment was less accurate in different-eye condition than the other conditions. In Experiment 2, the first circle array was split into a large-variance and a small-variance set, with either the large-variance or small-variance set preceding the presentation of the second circle array in the same eye. The variance of the first array was judged larger when the second array was preceded by the large-variance set in the same eye, showing that the perception of variance was modulated by the visual variance processed in the same eye. Taken together, these findings provide evidence for monocular processing of visual variance, suggesting that subcortical structures capture the statistical structure of the visual world.

An ON-type direction-selective ganglion cell in primate retina

To maintain a stable and clear image of the world, our eyes reflexively follow the direction in which a visual scene is moving. Such gaze-stabilization mechanisms reduce image blur as we move in the environment. In non-primate mammals, this behaviour is initiated by retinal output neurons called ON-type direction-selective ganglion cells (ON-DSGCs), which detect the direction of image motion and transmit signals to brainstem nuclei that drive compensatory eye movements1. However, ON-DSGCs have not yet been identified in the retina of primates, raising the possibility that this reflex is mediated by cortical visual areas. Here we mined single-cell RNA transcriptomic data from primate retina to identify a candidate ON-DSGC. We then combined two-photon calcium imaging, molecular identification and morphological analysis to reveal a population of ON-DSGCs in the macaque retina. The morphology, molecular signature and GABA (γ-aminobutyric acid)-dependent mechanisms that underlie direction selectivity in primate ON-DSGCs are highly conserved with those in other mammals. We further identify a candidate ON-DSGC in human retina. The presence of ON-DSGCs in primates highlights the need to examine the contribution of subcortical retinal mechanisms to normal and aberrant gaze stabilization in the developing and mature visual system.

A randomized controlled trial of Deep Brain Reorienting: a neuroscientifically guided treatment for post-traumatic stress disorder

ABSTRACT Background: Advanced neuroscientific insights surrounding post-traumatic stress disorder (PTSD) and its associated symptomatology should beget psychotherapeutic treatments that integrate these insights into practice. Deep Brain Reorienting (DBR) is a neuroscientifically-guided psychotherapeutic intervention that targets the brainstem-level neurophysiological sequence that transpired during a traumatic event. Given that contemporary treatments have non-response rates of up to 50% and high drop-out rates of >18%, DBR is investigated as a putative candidate for effective treatment of some individuals with PTSD. Objective: To conduct an interim evaluation of the effectiveness of an eight-session clinical trial of videoconference-based DBR versus waitlist (WL) control for individuals with PTSD. Method: Fifty-four individuals with PTSD were randomly assigned to DBR (N = 29) or WL (N = 25). At baseline, post-treatment, and three-month follow-up, participants’ PTSD symptom severity was assessed using the Clinician Administered PTSD Scale (CAPS-5). This is an interim analysis of a clinical trial registered with the U. S. National Institute of Health (NCT04317820). Results: Significant between-group differences in CAPS-total and all subscale scores (re-experiencing, avoidance, negative alterations in cognitions/mood, alterations in arousal/reactivity) were found at post-treatment (CAPS-total: Cohen’s d = 1.17) and 3-month-follow-up (3MFU) (CAPS-total: Cohen’s d = 1.18). Significant decreases in CAPS-total and all subscale scores were observed within the DBR group pre – to post-treatment (36.6% CAPS-total reduction) and pre-treatment to 3MFU (48.6% CAPS-total reduction), whereas no significant decreases occurred in the WL group. After DBR, 48.3% at post-treatment and 52.0% at 3MFU no longer met PTSD criteria. Attrition was minimal with one participant not completing treatment; eight participants were lost to 3MFU. Conclusions: These findings provide emerging evidence for the effectiveness of DBR as a well-tolerated treatment that is based on theoretical advances highlighting alterations to subcortical mechanisms in PTSD and associated symptomatology. Additional research utilizing larger sample sizes, neuroimaging data, and comparisons or adjacencies with other psychotherapeutic approaches is warranted. Trial registration: ClinicalTrials.gov identifier: NCT04317820..

Play and tickling responses map to the lateral columns of the rat periaqueductal gray

The persistence of play after decortication points to a subcortical mechanism of play control. We found that global blockade of the rat periaqueductal gray with either muscimol or lidocaine interfered with ticklishness and play. We recorded vocalizations and neural activity from the periaqueductal gray of young, playful rats during interspecific touch, play, and tickling. Rats vocalized weakly to touch and more strongly to play and tickling. Periaqueductal gray units showed diverse but strong modulation to tickling and play. Hierarchical clustering based on neuronal responses to play and tickling revealed functional clusters mapping to different periaqueductal gray columns. Specifically, we observed play-neutral/tickling-inhibited and tickling/play-neutral units in dorsolateral and dorsomedial periaqueductal gray columns. In contrast, strongly play/tickling-excited units mapped to the lateral columns and were suppressed by anxiogenic conditions. Optogenetic inactivation of lateral periaqueductal columns disrupted ticklishness and play. We conclude that the lateral periaqueductal gray columns are decisive for play and laughter.

The cognitive stability of an elderly human is guaranteed by his lifelong motor activity

A persons muscular activity, or behavior when performing various types of physical exercises, is determined by the brains complex, multi-level architectonics. The organization of any type of movement in sports and physical exercises, as well as various types of professional motor activity, involves all levels of the central nervous system.
 This study aims to analyze the benefits of sports for maintaining long-term brain activity.
 This study conducted literary critical analysis of the functional interaction of various cortical and subcortical mechanisms of human voluntary movements with domestic and foreign literature involvement.
 Regular sports cause structural changes in areas of the brain that are directly or indirectly involved in the organization of movements. Moreover, due to an increase in perfusion, a significant part of the gray matter of the primary sensorimotor fields and many associative areas of the cortex are also subject to structural changes. Muscle work and any motor activity are a positive factor that determines a persons cognitive stability in old age due to favorable changes in the brain.
 This conclusion refutes the popular belief that long-term sports lead to the preservation of only the motor cortex with age, whereas the capillary networks in other areas, particularly associative fields, occlude earlier with age, and impair intelligence.

Protracted development of motor cortex constrains rich interpretations of infant cognition.

Cognition in preverbal human infants must be inferred from overt motor behaviors such as gaze shifts, head turns, or reaching for objects. However, infant mammals - including human infants - show protracted postnatal development of cortical motor outflow. Cortical control of eye, face, head, and limb movements is absent at birth and slowly emerges over the first postnatal year and beyond. Accordingly, the neonatal cortex in humans cannot generate the motor behaviors routinely used to support inferences about infants' cognitive abilities, and thus claims of developmental continuity between infant and adult cognition are suspect. Recognition of the protracted development of motor cortex should temper rich interpretations of infant cognition and motivate more serious consideration of the role of subcortical mechanisms in early cognitive development.

Особливості VR-реабілітації у пацієнтів з хворобою Паркінсона

The purpose of the study was to determine the possibilities and effectiveness of VR rehabilitation in patients with Parkinson's disease compared to conventional rehabilitation intervention according to literature sources. Materials and methods. The study was carried out based on the results of the research and analysis of existing global scientific studies with the establishment of the possibilities and effectiveness of VR rehabilitation in patients with Parkinson's disease compared to the usual rehabilitation intervention. The search for information was performed using domestic and foreign Internet resources such as Google Scholar, PubMed, Medscape, Scopus, Web of Science databases, etc. Results and discussion. Treatment for Parkinson's disease is aimed at restoring motor and non-motor manifestations, which is corrected by appropriate pharmacological and surgical means, which are not fully effective without the addition of adequate rehabilitation interventions. Drug therapy is effective only in the first stages of the disease (some disorders do not respond to pharmacological agents at all); and deep stimulation of the affected area of the brain by implanting electrodes with their incorrect intraoperative location or incorrect stimulation parameters can provoke additional motor and sensory disorders and other adverse reactions. Physical rehabilitation in Parkinson's disease is an effective addition to drug therapy and surgery, and a long-term rehabilitation intervention effectively improves motor skills and cognitive abilities in this disease. In Parkinson's disease, rehabilitative measures aimed at motor-cognitive interactions are more useful in the early stages, which makes it possible to improve motor skills and general daily activities of the patient in real life. However, with the progression of Parkinson's disease, motor-cognitive impairments significantly limit the ability to learn, so it is directed at altered subcortical and cortical mechanisms of plasticity, which makes patients especially dependent on external sources of feedback. This problem is quite well leveled by the use of VR rehabilitation mechanisms. The effectiveness of rehabilitation with VR methodology in Parkinson's disease is determined by the need to take into account the arising sensory-motor and cognitive disorders, accurate assessment of the effectiveness of rehabilitation measures, optimized adaptation and safety for the patient himself. Conclusion. When determining the possibilities of VR rehabilitation technologies in patients with Parkinson's disease compared to conventional rehabilitation intervention, it was determined that these technologies are the most promising methods of treatment and rehabilitation intervention and an effective tool for the revitalization of disorders, have a number of advantages in the rehabilitation of gait and balance disorders, cognitive shifts, improving the quality of life and daily activities of patients, leveling neuropsychic symptoms, improving the plasticity of motor nerves and muscle control

Evolving changes in cortical and subcortical excitability during movement preparation: A study of brain potentials and eye-blink reflexes during loud acoustic stimulation.

During preparation for action, the presentation of loud acoustic stimuli (LAS) can trigger movements at very short latencies in a phenomenon called the StartReact effect. It was initially proposed that a special, separate subcortical mechanism that bypasses slower cortical areas could be involved. We sought to examine the evidence for a separate mechanism against the alternative that responses to LAS can be explained by a combination of stimulus intensity effects and preparatory states. To investigate whether cortically mediated preparatory processes are involved in mediating reactions to LAS, we used an auditory reaction task where we manipulated the preparation level within each trial by altering the conditional probability of the imperative stimulus. We contrasted responses to non-intense tones and LAS and examined whether cortical activation and subcortical excitability and motor responses were influenced by preparation levels. Increases in preparation levels were marked by gradual reductions in reaction time (RT) coupled with increases in cortical activation and subcortical excitability - at both condition and trial levels. Interestingly, changes in cortical activation influenced motor and auditory but not visual areas - highlighting the widespread yet selective nature of preparation. RTs were shorter to LAS than tones, but the overall pattern of preparation level effects was the same for both stimuli. Collectively, the results demonstrate that LAS responses are indeed shaped by cortically mediated preparatory processes. The concurrent changes observed in brain and behavior with increasing preparation reinforce the notion that preparation is marked by evolving brain states which shape the motor system for action.

Clinical-neuroimaging-pathological relationship analysis of adult onset Neuronal Intranuclear Inclusion Disease (NIID)

BackgroundNeuronal Intranuclear Inclusion Disease (NIID) is a degenerative disease with heterogeneous clinical manifestations. We aim to analysis the relationship between clinical manifestations, neuroimaging and skin pathology in a Chinese NIID cohort.MethodsPatients were recruited from a Chinese cohort. Detail clinical information were collected. Visual rating scale was used for evaluation of neuroimaging. The relationship between clinical presentations and neuroimaging, as well as skin pathology was statistically analyzed.ResultsThirty-two patients were recruited. The average onset age was 54.3 y/o. 28.1% had positive family history. Dementia, autonomic nervous system dysfunction, episodic attacks were three main presentations. CSF analysis including Aβ42 and tau level was almost normal. The most frequently involved on MRI was periventricular white matter (100%), frontal subcortical and deep white matter (96.6%), corpus callosum (93.1%) and external capsule (72.4%). Corticomedullary junction DWI high intensity was found in 87.1% patients. Frontal and external capsule DWI high intensity connected to form a “kite-like” specific image. Severity of dementia was significantly related to leukoencephalopathy (r = 0.465, p = 0.0254), but not cortical atrophy and ventricular enlargement. Grey matter lesions were significantly associated with encephalopathy like attacks (p = 0.00077) but not stroke like attacks. The density of intranuclear inclusions in skin biopsy was not associated with disease duration, severity of leukoencephalopathy and dementia.ConclusionsSpecific distribution of leukoencephalopathy and DWI high intensity were indicative. Leukoencephalopathy and subcortical mechanism were critical in pathogenesis of NIID. Irrelevant of inclusion density and clinical map suggested the direct pathogenic factor need further investigation.

Decoding fear of negative evaluation from brain morphology: A machine‐learning study on structural neuroimaging data

BackgroundFear of negative evaluation (FNE), referring to negative expectation and feelings toward other people’s social evaluation, is closely associated with social anxiety that plays an important role in our social life. Exploring the neural markers of FNE may be of theoretical and practical significance to psychiatry research ( e.g., studies on social anxiety).MethodsTo search for potentially relevant biomarkers of FNE in human brain, the current study applied multivariate relevance vector regression, a machine‐learning and data‐driven approach, on brain morphological features ( e.g., cortical thickness) derived from structural imaging data; further, we used these features as indexes to predict self‐reported FNE score in each participant.ResultsOur results confirm the predictive power of multiple brain regions, including those engaged in negative emotional experience ( e.g., amygdala, insula), regulation and inhibition of emotional feeling ( e.g., frontal gyrus, anterior cingulate gyrus), and encoding and retrieval of emotional memory ( e.g., posterior cingulate cortex, parahippocampal gyrus).ConclusionsThe current findings suggest that anxiety represents a complicated construct that engages multiple brain systems, from primitive subcortical mechanisms to sophisticated cortical processes.

Spread of pathological human Tau from neurons to oligodendrocytes and loss of high-firing pyramidal neurons in aging mice.

Intracellular aggregation of hyperphosphorylated Tau (pTau) in the brain is associated with cognitive and motor impairments, and ultimately neurodegeneration. We investigate how human pTau affects cells and network activity in the hippocampal formation of the THY-Tau22 tauopathy model mice invivo. We find that pTau preferentially accumulates in deep-layer pyramidal neurons, leading to neurodegeneration, and we establish that pTau spreads to oligodendrocytes. During goal-directed virtual navigation in aged transgenic mice, we detect fewer high-firing prosubicular pyramidal cells, but the firing population retains its coupling to theta oscillations. Analysis of network oscillations and firing patterns of pyramidal and GABAergic neurons recorded in head-fixed and freely moving mice suggests preserved neuronal coordination. In spatial memory tests, transgenic mice have reduced short-term familiarity, but spatial working and reference memory are surprisingly normal. We hypothesize that unimpaired subcortical network mechanisms maintain cortical neuronal coordination, counteracting the widespread pTau aggregation, loss of high-firing cells, and neurodegeneration.

Reward Enhances Memory via Age-Varying Online and Offline Neural Mechanisms across Development.

Reward motivation enhances memory through interactions between mesolimbic, hippocampal, and cortical systems, both during and after encoding. Developmental changes in these distributed neural circuits may lead to age-related differences in reward-motivated memory and the underlying neural mechanisms. Converging evidence from cross-species studies suggests that subcortical dopamine signaling is increased during adolescence, which may lead to stronger memory representations of rewarding, relative to mundane, events and changes in the contributions of underlying subcortical and cortical brain mechanisms across age. Here, we used fMRI to examine how reward motivation influences the "online" encoding and "offline" postencoding brain mechanisms that support long-term associative memory from childhood to adulthood in human participants of both sexes. We found that reward motivation led to both age-invariant enhancements and nonlinear age-related differences in associative memory after 24 h. Furthermore, reward-related memory benefits were linked to age-varying neural mechanisms. During encoding, interactions between the prefrontal cortex (PFC) and ventral tegmental area (VTA) were associated with better high-reward memory to a greater degree with increasing age. Preencoding to postencoding changes in functional connectivity between the anterior hippocampus and VTA were also associated with better high-reward memory, but more so at younger ages. Our findings suggest that there may be developmental differences in the contributions of offline subcortical and online cortical brain mechanisms supporting reward-motivated memory.SIGNIFICANCE STATEMENT A substantial body of research has examined the neural mechanisms through which reward influences memory formation in adults. However, despite extensive evidence that both reward processing and associative memory undergo dynamic change across development, few studies have examined age-related changes in these processes. We found both age-invariant and nonlinear age-related differences in reward-motivated memory. Moreover, our findings point to developmental differences in the processes through which reward modulates the prioritization of information in long-term memory, with greater early reliance on offline subcortical consolidation mechanisms and increased contribution of systems-level online encoding circuitry with increasing age. These results highlight dynamic developmental changes in the cognitive and neural mechanisms through which motivationally salient information is prioritized in memory from childhood to adulthood.

Boosted dopamine and blunted serotonin in Tourette syndrome- evidence from in vivo imaging studies.

The precise cortical and subcortical mechanisms of Tourette syndrome (TS) are still not fully understood. In the present retrospective analysis, adolescent and adult medication-naïve patients showed increased DA transporter (DAT) binding in nucleus caudate (CAUD), putamen (PUT) and/or whole neostriatum (NSTR). D2 receptor (R)binding and DA release were not different from controls throughout the nigrostriatal and mesolimbocortical system. When patients were medication-free (either medication-naïve or under withdrawal), DAT was still increased in PUT, but not different from controls in CAUD, NSTR and ventral striatum (VSTR). SERT was unaltered in midbrain/pons (MP), but decreased in PUT, thalamus (THAL) and hypothalamus. D2R was unaltered throughout the nigrostriatal and mesolimbocortical system, while DA release was not different from controls in PUT, CAUD and NSTR, but elevated in VSTR. 5-HT2AR binding was unaltered in neocortex and cingulate. In acutely medicated adults, DAT was unaltered in PUT, but still increased in CAUD, whereas DA release remained unaltered throughout the nigrostriatal and mesolimbocortical system. When part of the patients was acutely medicated, vesicular monoamine transporter (VMAT2), DAT, SERT and DA synthesis were not different from controls in striatal regions, whereas D2R was decreased in NSTR, THAL, frontal cortex and limbic regions. Conversely, 5-HT2AR binding was unaltered in striatal regions and THAL, but increased in neocortical and limbic areas. It may be hypothesized that both the DA surplus and the 5-HT shortage in key regions of the nigrostriatal and mesolimbic system are relevant for the bouts of motor activity and the deficiencies in inpulse control.

Temporal dynamics of the neural representation of hue and luminance polarity

Hue and luminance contrast are basic visual features. Here we use multivariate analyses of magnetoencephalography data to investigate the timing of the neural computations that extract them, and whether they depend on common neural circuits. We show that hue and luminance-contrast polarity can be decoded from MEG data and, with lower accuracy, both features can be decoded across changes in the other feature. These results are consistent with the existence of both common and separable neural mechanisms. The decoding time course is earlier and more temporally precise for luminance polarity than hue, a result that does not depend on task, suggesting that luminance contrast is an updating signal that separates visual events. Meanwhile, cross-temporal generalization is slightly greater for representations of hue compared to luminance polarity, providing a neural correlate of the preeminence of hue in perceptual grouping and memory. Finally, decoding of luminance polarity varies depending on the hues used to obtain training and testing data. The pattern of results is consistent with observations that luminance contrast is mediated by both L-M and S cone sub-cortical mechanisms.

Duration of postictal impaired awareness after bilateral tonic-clonic seizures: EEG and patient characteristics

ObjectiveIctal and postictal phenomena that may impact the duration of postictal impaired awareness have not been well studied. Postictal unresponsiveness invariably occurs following bilateral tonic-clonic seizures (BTCS). Bilateral tonic-clonic seizures are a major risk factor for sudden unexpected death in epilepsy (SUDEP). We quantify the effects of seizure characteristics on postictal recovery of awareness following BTCS. Factors include: the total seizure duration, the duration of the tonic phase of a BTCS, presence of postictal generalized EEG suppression (PGES), duration of postictal tonic electromyographic discharge, peri-ictal respiratory dysfunction, patient age, duration of epilepsy, and gender. MethodsFifty-eight patients admitted to the epilepsy monitoring unit with BTCS were studied. Forty-one had unilateral onset temporal seizures. The remainder had bitemporal onsets, extratemporal onsets, undetermined onsets, or were generalized at onset. Following the first BTCS, time to initial recovery of awareness and its possible association with patient and seizure characteristics as well as peri-ictal respiratory dysfunction were evaluated. The presence or absence of postictal agitation was noted. ResultsThe severity of respiratory dysfunction and seizure characteristics were not associated with time to initial recovery of awareness. A shorter time to recovery of awareness was significantly associated with a younger age (p = 0.007). Postictal agitation was more common in males (p = 0.023). SignificanceFocal seizures may impair awareness by active inhibition of subcortical arousal mechanisms. Focal seizures progressing to bilateral tonic-clonic seizures (BTCS) result in further widespread cerebral dysfunction impacting postictal awareness. MRI studies show accelerated brain aging in patients with temporal lobe epilepsy. Our findings suggest that patient age, as a surrogate marker for the lifetime burden of seizures, results in a progressive worsening in time to recovery after BTCS by an increasing negative impact on networks involved in arousal.

The neurophysiology of pursuit.

This chapter summarizes early electrophysiological and lesion studies to elucidate cortical, subcortical and cerebellar mechanisms for extracting visual target motion and programming a smooth-pursuit response. The importance of a descending pursuit pathway from the middle temporal (MT) cortical visual area, which extracts the speed and direction of a moving target, the projections to dorsolateral pontine nuclei, and onto the cerebellum are outlined. Contributions of the cerebellum to pursuit are discussed and models are presented to account for the ways in which floccular gaze Purkinje cells behave during smooth pursuit, combined eye-head tracking, and during head rotation while viewing a stationary target.