[Simultanagnosia caused by cerebral infarction in the right temporal stem, right lateral thalamus, and right pulvinar regions].

A 76-year-old male patient was admitted to our hospital for the treatment of acute cerebral infarction in the right temporal stem, right lateral thalamus, and right pulvinar regions. Although his overall cognitive function was almost normal, he exhibited reduced visual sensitivity in the homonymous lower left quadrant of the visual field, left unilateral spatial neglect (USN), and simultanagnosia. Left USN improved 4 months after the onset of infarction; however, simultanagnosia persisted. To the best of our knowledge, this is the first case of simultanagnosia caused by cerebral infarction in the right temporal stem, right lateral thalamus, and right pulvinar regions.

Modulation of pulvinar connectivity with cortical areas in the control of selective visual attention.

Selective attention mechanisms operate across large-scale cortical networks by amplifying behaviorally relevant sensory information while suppressing interference from distractors. Although it is known that fronto-parietal regions convey information about attentional priorities, it is unclear how such cortical communication is orchestrated. Based on its unique connectivity pattern with the cortex, we hypothesized that the pulvinar, a nucleus of the thalamus, may play a key role in coordinating and modulating remote cortical activity during selective attention. By using a visual task that orthogonally manipulated top-down selection and bottom-up competition during functional MRI, we investigated the modulations induced by task-relevant (spatial cue) and task-irrelevant but salient (distractor) stimuli on functional interactions between the pulvinar, occipito-temporal cortex, and frontoparietal areas involved in selective attention. Pulvinar activity and connectivity were distinctively modulated during the co-occurrence of the cue and salient distractor stimuli, as opposed to the presence of one of these factors alone. Causal modelling analysis further indicated that the pulvinar acted by weighting excitatory signals to cortical areas, predominantly in the presence of both the cue and the distractor. These results converge to support a pivotal role of the pulvinar in integrating top-down and bottom-up signals among distributed networks when confronted with conflicting visual stimuli, and thus contributing to shape priority maps for the guidance of attention.

Microsurgical approaches to the pulvinar: A comparative analysis.

OBJECTIVE: To compare the area of exposure to the cisternal thalamus associated with four surgical techniques: supracerebellar-infratentorial (SCIT), occipital interhemispheric (OI), transchoroidal (TC) and subtemporal before and after parahippocampal resection (ST and STh, respectively). METHODS: All approaches were performed on both sides of three heads. Qualitative anatomical analyses were performed to understand anatomical limits, advantages, and flaws of each technique. Quantitative analyses for multiple repeated dependent variables assessed significant differences between areas of exposure. RESULTS: Exposure area was significantly more extensive using TC and STh approaches compared to ST, OI, and SCIT. STh achieved a significantly wider exposure compared to ST. Regarding dissection angle, surrounding structures and limitations, ST approaches do not provide adequate exposure, nor alignment with the thalamic axis. The OI and STh may provide a better field of exposure, but without adequate alignment and challenging deeper dissections. TC provides better exposure of the cisternal pulvinar with access to lateral pulvinar at the atrium's anterior wall but is a transcortical route that disrupts non-pathological tissue. SCIT provides an adequate area of exposure with the possibility of alignment with the thalamus axis, thus allowing an easier dissection of deeper lesions. CONCLUSIONS: For lesions at the pulvinar surface, OI and STh are adequate. For lesions restricted to medial pulvinar and deep along the thalamus axis, SCIT approaches are recommended. Lesions extending to the lateral pulvinar and ventricular atrium are best removed through TC approaches. The ST approach was not suitable to the cisternal pulvinar due to its limited angular exposure.

Development of thalamus mediates paternal age effect on offspring reading: A preliminary investigation.

The importance of (inherited) genetic impact in reading development is well established. De novo mutation is another important contributor that is recently gathering interest as a major liability of neurodevelopmental disorders, but has been neglected in reading research to date. Paternal age at childbirth (PatAGE) is known as the most prominent risk factor for de novo mutation, which has been repeatedly shown by molecular genetic studies. As one of the first efforts, we performed a preliminary investigation of the relationship between PatAGE, offspring's reading, and brain structure in a longitudinal neuroimaging study following 51 children from kindergarten through third grade. The results showed that greater PatAGE was significantly associated with worse reading, explaining an additional 9.5% of the variance after controlling for a number of confounds-including familial factors and cognitive-linguistic reading precursors. Moreover, this effect was mediated by volumetric maturation of the left posterior thalamus from ages 5 to 8. Complementary analyses indicated the PatAGE-related thalamic region was most likely located in the pulvinar nuclei and related to the dorsal attention network by using brain atlases, public datasets, and offspring's diffusion imaging data. Altogether, these findings provide novel insights into neurocognitive mechanisms underlying the PatAGE effect on reading acquisition during its earliest phase and suggest promising areas of future research.

The Role of the Thalamus in Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) has a high lifetime prevalence and is one of the more serious challenges in mental health care. Fear-conditioned learning involving the amygdala has been thought to be one of the main causative factors; however, recent studies have reported abnormalities in the thalamus of PTSD patients, which may explain the mechanism of interventions such as eye movement desensitization and reprocessing (EMDR). Therefore, I conducted a miniature literature review on the potential contribution of the thalamus to the pathogenesis of PTSD and the validation of therapeutic approaches. As a result, we noticed the importance of the retinotectal pathway (superior colliculus-pulvinar-amygdala connection) and discussed therapeutic indicators.

Intrinsic and Extrinsic Mechanisms of Thalamic Pathology in Multiple Sclerosis.

OBJECTIVE: Thalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong predictor of disability progression. The causes of thalamic atrophy are not fully understood. Here, we investigate the contributions of thalamic demyelinated lesions, thalamic neuronal loss, and cerebral white matter (WM) lesions to thalamic volume. METHODS: We used postmortem in situ magnetic resonance imaging (MRI) scans of 95 subjects with MS to correlate thalamic lesion volumes with global MRI metrics. We histologically characterized thalamic demyelination patterns and compared neuronal loss and neuritic pathology in the thalami with the extremes of volume. RESULTS: Grossly apparent thalamic discolorations in cm-thick brain slices were T2/fluid-attenuated inversion recovery (FLAIR) hyperintense, T1-hypointense, and appeared as perivascular demyelinated lesions with dystrophic neurons/axons. Subependymal demyelinated lesions with axonal loss and microglial/macrophage activation were also observed. The 12 subjects with the least thalamic volume had a 17.6% reduction of median neuronal density in the dorsomedial/ventrolateral and pulvinar nuclei compared with the 14 subjects with the greatest thalamic volume (p = 0.03). After correcting for age, disease duration, sex, and T2 lesion volume, the total (p = 0.20), ovoid (p = 0.31), or subependymal (p = 0.44) MRI thalamic lesion volumes correlated with thalamic volume. Thalamic volume correlated with cerebral T2 lesion volume (Spearman's rho = -0.65, p < 0.001; p < 0.0001 after correcting for age, disease duration, and sex). INTERPRETATION: Our findings suggest the degeneration of efferent/afferent thalamic projections and/or a neurodegenerative process as greater contributors to thalamic atrophy than thalamic demyelinating lesions. ANN NEUROL 2020 ANN NEUROL 2020;88:81-92.

Thalamic-Medial Temporal Lobe Connectivity Underpins Familiarity Memory.

The neural basis of memory is highly distributed, but the thalamus is known to play a particularly critical role. However, exactly how the different thalamic nuclei contribute to different kinds of memory is unclear. Moreover, whether thalamic connectivity with the medial temporal lobe (MTL), arguably the most fundamental memory structure, is critical for memory remains unknown. We explore these questions using an fMRI recognition memory paradigm that taps familiarity and recollection (i.e., the two types of memory that support recognition) for objects, faces, and scenes. We show that the mediodorsal thalamus (MDt) plays a material-general role in familiarity, while the anterior thalamus plays a material-general role in recollection. Material-specific regions were found for scene familiarity (ventral posteromedial and pulvinar thalamic nuclei) and face familiarity (left ventrolateral thalamus). Critically, increased functional connectivity between the MDt and the parahippocampal (PHC) and perirhinal cortices (PRC) of the MTL underpinned increases in reported familiarity confidence. These findings suggest that familiarity signals are generated through the dynamic interaction of functionally connected MTL-thalamic structures.

Abnormal thalamocortical network dynamics in migraine.

OBJECTIVE: To investigate the dynamic functional connectivity of thalamocortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity. METHODS: We investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate linear regression model. RESULTS: Five dFNC brain states were identified to characterize and compare dynamic functional connectivity patterns. We demonstrated that migraineurs spent more time in a strongly interconnected between-network state, but they spent less time in a sparsely connected state. Interestingly, we found that abnormal posterior thalamus (pulvinar nucleus) dFNC with the visual cortex and the precuneus were significantly correlated with headache frequency of migraine. Further topologic measures revealed that migraineurs had significantly lower efficiency of information transfer in both global and local dFNC. CONCLUSION: Our results demonstrated a transient pathologic state with atypical thalamocortical connectivity in migraineurs and extended current findings regarding abnormal thalamocortical networks and dysrhythmia in migraine.

Preliminary report on the association between pulvinar volume and the ability to detect backward-masked facial features.

Although backward masking is a powerful experimental tool in mitigating visual awareness of facial expressions of emotion, ~20% of participants consistently report being resistant to its effects. In our previous studies, we excluded these participants from analysis as we focused on neural data in individuals who were subjectively unaware of backward-masked facial features that were presented for a brief period of time (e.g., 17ms). Here, we shifted our focus to potential structural brain difference between aware and unaware participants. To achieve this, structural magnetic resonance imaging (sMRI) data were pooled from two recent backward masking studies of emotional faces or eye whites (Kim et al., 2016, 2010). Out of a total of 64 participants, 12 reported being subjectively aware of the masked faces or their facial features. Whole-brain, voxel-based morphometric analysis of structural MRI data yielded significantly greater volume of the posterior thalamus, including the bilateral pulvinar, for the subjectively aware versus unaware individuals. No other brain region showed significant volumetric differences between groups. The present findings offer a neuroanatomical basis for visual awareness of emotional content in the form of backward-masked facial features, which complements the known functional role of the pulvinar in such neurobehavioral processes.

The pulvinar nucleus and antidepressant treatment: dynamic modeling of antidepressant response and remission with ultra-high field functional MRI.

Functional magnetic resonance imaging (fMRI) successfully disentangled neuronal pathophysiology of major depression (MD), but only a few fMRI studies have investigated correlates and predictors of remission. Moreover, most studies have used clinical outcome parameters from two time points, which do not optimally depict differential response times. Therefore, we aimed to detect neuronal correlates of response and remission in an antidepressant treatment study with 7 T fMRI, potentially harnessing advances in detection power and spatial specificity. Moreover, we modeled outcome parameters from multiple study visits during a 12-week antidepressant fMRI study in 26 acute (aMD) patients compared to 36 stable remitted (rMD) patients and 33 healthy control subjects (HC). During an electrical painful stimulation task, significantly higher baseline activity in aMD compared to HC and rMD in the medial thalamic nuclei of the pulvinar was detected (p = 0.004, FWE-corrected), which was reduced by treatment. Moreover, clinical response followed a sigmoid function with a plateau phase in the beginning, a rapid decline and a further plateau at treatment end. By modeling the dynamic speed of response with fMRI-data, perigenual anterior cingulate activity after treatment was significantly associated with antidepressant response (p < 0.001, FWE-corrected). Temporoparietal junction (TPJ) baseline activity significantly predicted non-remission after 2 antidepressant trials (p = 0.005, FWE-corrected). The results underline the importance of the medial thalamus, attention networks in MD and antidepressant treatment. Moreover, by using a sigmoid model, this study provides a novel method to analyze the dynamic nature of response and remission for future trials.

Heterogeneity of anatomic regions by MR volumetry in juvenile myoclonic epilepsy.

OBJECTIVE: To investigate brain volumes in patients with well-characterized juvenile myoclonic epilepsy (JME). MATERIALS AND METHODS: We studied the MRI images of seventeen subjects with EEG and clinically defined JME and seventeen age- and sex-matched controls using voxel-based morphometry (VBM) and automated and manual volumetry. RESULTS: We found no significant group differences in the cortical volumes by automated techniques for all regions or for the whole brain. However, we found a larger pulvinar nucleus in JME using VBM with small volume correction and a larger thalamus with manual volumetry (P = 0.001; corrected two-tailed t-test). By analysing the individual subjects, we determined that considerable heterogeneity exists even in this highly selected group. Histograms of all JME and matched control regions' volumes showed more subjects with JME had smaller hippocampi and larger thalami (P < 0.05; chi-square). Subjects in whom the first seizure was absence were more likely to have smaller hippocampi than their matched control, while those without absences showed no differences (P < 0.05, chi-square). CONCLUSIONS: There is ample evidence for frontal cortical thalamic network changes in JME, but subcortical structural differences were more distinct in this group. Given the heterogeneity of brain volumes in the clinical population, further advancement in the field will require the examination of stringent genetically controlled populations.

Brain MRI findings in aspartylglucosaminuria.

BACKGROUND AND PURPOSE: The aim of this study was to identify characteristic 3.0 T brain MRI findings in patients with aspartylglucosaminuria (AGU), a rare lysosomal storage disorder. Previous AGU patient material imaged at 1.0 and 1.5 T was also re-evaluated. MATERIALS AND METHODS: Twenty-five brain MRI examinations from 20 AGU patients were included in the study. Thirteen patients underwent a prospective 3.0 T MRI (5 male, 8 female, aged 9-45 years). Twelve examinations from nine patients (4 male, 5 female, aged 8-33 years) previously imaged at 1.0 or 1.5 T were re-evaluated. Two patients were included in both the prospective and the retrospective groups. Visual analysis of the T1- and T2-weighted images was performed by two radiologists. RESULTS: The previously reported signal intensity changes in T2-weighted images were visible at all field strengths, but they were more distinct at 3.0 T than at 1.0 or 1.5 T. These included signal intensity decrease in the thalami and especially in the pulvinar nuclei, periventricular signal intensity increase and juxtacortical high signal foci. Poor differentiation between gray and white matter was found in all patients. Some degree of cerebral and/or cerebellar atrophy and mild ventricular dilatation were found in nearly all patients. This study also disclosed various unspecific findings, including a higher than normal incidence of dilated perivascular spaces, arachnoid cysts, pineal cysts and mildly dilated cavum veli interpositi. CONCLUSION: This study revealed particular brain MRI findings in AGU, which can raise the suspicion of this rare disease in clinical practice.

Differentiating attention-deficit/hyperactivity disorder inattentive and combined types: a (1)H-magnetic resonance spectroscopy study of fronto-striato-thalamic regions.

Despite the implication of fronto-striatal circuits in attention-deficit/hyperactivity disorder (ADHD), there is a lack of information on the role of these regions, especially the thalamus, in the heterogeneity of ADHD. We assessed the (1)H-magnetic resonance spectroscopy profile in ventromedial prefrontal cortex (VMPFC)-thalamic-striatal regions bilaterally in three groups of subjects (age range 18-24 years old): ADHD inattentive type (ADHD-I; n = 9), ADHD combined type (ADHD-C; n = 10) and non-ADHD controls (n = 12). The peaks of N-acetylaspartate, Choline (Cho), myo-inositol (mI), creatine (Cr) and glutamate-glutamine-GABA (Glx) to Cr were calculated. Subjects with ADHD-C showed lower mI/Cr ratio in the right VMPFC than controls, higher Cho/Cr ratio in the left thalamus-pulvinar than the ADHD-I group and higher Glx/Cr ratio in left putamen than individuals with ADHD-I and controls. This metabolic profile suggests a disruption of fronto-striato-thalamic structures in the ADHD-C as a result of lower neuronal energetic metabolism.

Pattern-motion selectivity in the human pulvinar.

On the basis of anatomical and physiological data obtained on animal models, we recently proposed that neurons in the main visual extrageniculate nuclei complex, the pulvinar, are actively involved in higher-order visual processing. Pulvinar neurons have been shown to integrate the component signals of a plaid pattern into a coherent global percept (pattern-motion selectivity). Using positron emission tomography (PET), we have investigated the possibility that the human pulvinar is also involved in plaid-defined higher-order motion integration. Plaid patterns were presented to normal observers in two conditions (coherent vs. transparent) created by varying the relative spatial frequency of the two gratings comprising the plaid. Regions of interest analysis revealed a significant activation of the pulvinar in the coherent condition supporting the notion that the human pulvinar nucleus is involved in higher-order motion processing. Plaid pattern activation was also observed in the medial temporal gyrus (area MT/V5), a motion area with strong anatomical connections to the pulvinar. These data provide the first direct evidence that the human pulvinar is involved in complex motion integration, as previously shown in animal models, and further support the existence of cortico-thalamo-cortical computational networks involved in higher-order visual processing.