Distinct neural signatures of pulvinar in C9orf72 amyotrophic lateral sclerosis mutation carriers and noncarriers.

BACKGROUND AND PURPOSE: Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal dementia-amyotrophic lateral sclerosis (ALS) spectrum. Specifically, the pulvinar, a high-order thalamic nucleus and timekeeper for large-scale cortical networks, has been hypothesized to be involved in C9orf72-related neurodegenerative diseases. We investigated whether pulvinar volume can be useful for differential diagnosis in ALS C9orf72 mutation carriers and noncarriers and how underlying functional connectivity changes affect this region. METHODS: We studied 19 ALS C9orf72 mutation carriers (ALSC9+) accurately matched with wild-type ALS (ALSC9-) and ALS mimic (ALSmimic) patients using structural and resting-state functional magnetic resonance imaging data. Pulvinar volume was computed using automatic segmentation. Seed-to-voxel functional connectivity analyses were performed using seeds from a pulvinar functional parcellation. RESULTS: Pulvinar structural integrity had high discriminative values for ALSC9+ patients compared to ALSmimic (area under the curve [AUC] = 0.86) and ALSC9- (AUC = 0.77) patients, yielding a volume cutpoint of approximately 0.23%. Compared to ALSmimic, ALSC9- showed increased anterior, inferior, and lateral pulvinar connections with bilateral occipital-temporal-parietal regions, whereas ALSC9+ showed no differences. ALSC9+ patients when compared to ALSC9- patients showed reduced pulvinar-occipital connectivity for anterior and inferior pulvinar seeds. CONCLUSIONS: Pulvinar volume could be a differential biomarker closely related to the C9orf72 mutation. A pulvinar-cortical circuit dysfunction might play a critical role in disease progression and development, in both the genetic phenotype and ALS wild-type patients.

Network Localization of Unconscious Visual Perception in Blindsight.

OBJECTIVE: Blindsight is a disorder where brain injury causes loss of conscious but not unconscious visual perception. Prior studies have produced conflicting results regarding the neuroanatomical pathways involved in this unconscious perception. METHODS: We performed a systematic literature search to identify lesion locations causing visual field loss in patients with blindsight (n = 34) and patients without blindsight (n = 35). Resting state functional connectivity between each lesion location and all other brain voxels was computed using a large connectome database (n = 1,000). Connections significantly associated with blindsight (vs no blindsight) were identified. RESULTS: Functional connectivity between lesion locations and the ipsilesional medial pulvinar was significantly associated with blindsight (family wise error p = 0.029). No significant connectivity differences were found to other brain regions previously implicated in blindsight. This finding was independent of methods (eg, flipping lesions to the left or right) and stimulus type (moving vs static). INTERPRETATION: Connectivity to the ipsilesional medial pulvinar best differentiates lesion locations associated with blindsight versus those without blindsight. Our results align with recent data from animal models and provide insight into the neuroanatomical substrate of unconscious visual abilities in patients. ANN NEUROL 2022;91:217-224.

Characterizing effects of age, sex and psychosis symptoms on thalamocortical functional connectivity in youth.

The thalamus is composed of multiple nuclei densely connected with the cortex in an organized manner, forming parallel thalamocortical networks critical to sensory, motor, and cognitive functioning. Thalamocortical circuit dysfunction has been implicated in multiple neurodevelopmental disorders, including schizophrenia, which also often exhibit sex differences in prevalence, clinical characteristics, and neuropathology. However, very little is known about developmental and sex effects on thalamocortical networks in youth. The present study characterized the effects of age, sex and psychosis symptomatology in anatomically constrained thalamocortical networks in a large community sample of youth (n = 1100, aged 8-21) from the Philadelphia Neurodevelopmental Cohort (PNC). Cortical functional connectivity of seven anatomically defined thalamic nuclear groups were examined: anterior, mediodorsal, ventral lateral, ventral posterolateral, pulvinar, medial and lateral geniculate nuclear groups. Age and sex effects were characterized using complementary thalamic region-of-interest (ROI) to cortical ROI and voxel-wise analyses. Effects of clinical symptomatology were analyzed by separating youth into three groups based on their clinical symptoms; typically developing youth (n = 298), psychosis spectrum youth (n = 320), and youth with other psychopathologies (n = 482). As an exploratory analysis, association with PRIME scores were used as a dimensional measure of psychopathology. Age effects were broadly characterized by decreasing connectivity with sensory/motor cortical areas, and increasing connectivity with heteromodal prefrontal and parietal cortical areas. This pattern was most pronounced for thalamic motor and sensory nuclei. Females showed greater connectivity between multiple thalamic nuclear groups and the visual cortex compared to males, while males showed greater connectivity with the inferior frontal and orbitofrontal cortices. Youth with psychosis spectrum symptoms showed a subtle decrease in thalamic connectivity with the premotor and prefrontal cortices. Across all youth, greater PRIME scores were associated with lower connectivity between the prefrontal cortex and mediodorsal thalamus. By characterizing typical development in anatomically constrained thalamocortical networks, this study provides an anchor for conceptualizing disruptions to the integrity of these networks observed in neurodevelopmental disorders.

Blindsight relies on a functional connection between hMT+ and the lateral geniculate nucleus, not the pulvinar.

When the primary visual cortex (V1) is damaged, the principal visual pathway is lost, causing a loss of vision in the opposite visual field. While conscious vision is impaired, patients can still respond to certain images; this is known as 'blindsight'. Recently, a direct anatomical connection between the lateral geniculate nucleus (LGN) and human motion area hMT+ has been implicated in blindsight. However, a functional connection between these structures has not been demonstrated. We quantified functional MRI responses to motion in 14 patients with unilateral V1 damage (with and without blindsight). Patients with blindsight showed significant activity and a preserved sensitivity to speed in motion area hMT+, which was absent in patients without blindsight. We then compared functional connectivity between motion area hMT+ and a number of structures implicated in blindsight, including the ventral pulvinar. Only patients with blindsight showed an intact functional connection with the LGN but not the other structures, supporting a specific functional role for the LGN in blindsight.

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.

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.

Severe hypersomnia after unilateral infarction in the pulvinar nucleus- a case report.

BACKGROUND: Although a central role of the thalamus for sleep regulation is undisputed, the exact localization of the crucial structures within the thalamus remains controversial. CASE PRESENTATION: Here we report a 35 year old woman with no prior comorbidities who developed severe and persistent hypersomnia with long sleep time after a small right-sided MRI-verified thalamic stroke affecting the dorsal part of the pulvinar and the dorsolateral boarders of the dorsomedial nuclei. CONCLUSION: The observed symptoms suggest a crucial role of posterior thalamus but not the midline parts of the thalamus in sleep-wake control.

The effect of medial pulvinar stimulation on temporal lobe seizures.

We investigated the effect of electrical stimulation of the medial pulvinar (PuM) in terms of its effect on temporal lobe seizures. Eight patients with drug-resistant temporal lobe epilepsy undergoing stereoelectroencephalographic exploration were included. All had at least one electrode exploring the PuM. High-frequency (50 Hz) stimulations of the PuM were well tolerated in the majority of them. During diagnostic stimulation to confirm the epileptogenic zone, 19 seizures were triggered by stimulating the hippocampus. During some of these seizures, ipsilateral pulvinar stimulation was applied (130 Hz, pulse width = 450 microseconds, duration = 3-7 seconds, 1-2 mA). Compared to non-PuM-stimulated seizures, five of eight patients experienced clinically less severe seizures, particularly in terms of degree of alteration of consciousness. On the electrical level, seizures were more rapidly clonic with a shorter tonic phase. This proof of concept study is the first to suggest that PuM stimulation could be a well-tolerated and effective means of therapeutic deep brain stimulation in drug-resistant epilepsies.

Resting-state pulvinar-posterior parietal decoupling in PTSD and its dissociative subtype.

Key evidence points toward alterations in the neurocircuitry of large-scale networks among patients with posttraumatic stress disorder (PTSD). The pulvinar is a thalamic region displaying reciprocal connectivity with the cortex and has been shown to modulate alpha synchrony to facilitate network communication. During rest, the pulvinar displays functional connectivity with the posterior parietal cortex (PPC), a heteromodal network of brain areas underlying multisensory integration and socioaffective functions that are shown at deficit in PTSD. Accordingly, this study seeks to reveal the resting-state functional connectivity (rsFC) patterns of individuals with PTSD, its dissociative subtype (PTSD + DS) and healthy controls. A whole-brain rsFC analysis was conducted using SPM12 and PickAtlas. Connectivity was analyzed for the left and right pulvinar across groups of individuals with PTSD (n = 81), PTSD + DS (n = 49), and controls (n = 51). As compared to PTSD, controls displayed significantly greater pulvinar rsFC with the superior parietal lobule and precuneus. Moreover, as compared to PTSD + DS, controls showed increased pulvinar connectivity with the superior parietal lobule, inferior parietal lobule and the precuneus. PTSD groups did not display stronger connectivity with any region as compared to controls. Last, PTSD had greater rsFC in the supramarginal gyrus relative to PTSD + DS. Reduced connectivity between the pulvinar and PPC may explain impairments to autobiographical memory, self-referential processing, and socioaffective domains in PTSD and PTSD + DS even at "rest." Critically, these alterations appear to be exacerbated in individuals with PTSD + DS, which may have important implications for treatment.

Connectivity between the superior colliculus and the amygdala in humans and macaque monkeys: virtual dissection with probabilistic DTI tractography.

It has been suggested that some cortically blind patients can process the emotional valence of visual stimuli via a fast, subcortical pathway from the superior colliculus (SC) that reaches the amygdala via the pulvinar. We provide in vivo evidence for connectivity between the SC and the amygdala via the pulvinar in both humans and rhesus macaques. Probabilistic diffusion tensor imaging tractography revealed a streamlined path that passes dorsolaterally through the pulvinar before arcing rostrally to traverse above the temporal horn of the lateral ventricle and connect to the lateral amygdala. To obviate artifactual connectivity with crossing fibers of the stria terminalis, the stria was also dissected. The putative streamline between the SC and amygdala traverses above the temporal horn dorsal to the stria terminalis and is positioned medial to it in humans and lateral to it in monkeys. The topography of the streamline was examined in relation to lesion anatomy in five patients who had previously participated in behavioral experiments studying the processing of emotionally valenced visual stimuli. The pulvinar lesion interrupted the streamline in two patients who had exhibited contralesional processing deficits and spared the streamline in three patients who had no deficit. Although not definitive, this evidence supports the existence of a subcortical pathway linking the SC with the amygdala in primates. It also provides a necessary bridge between behavioral data obtained in future studies of neurological patients, and any forthcoming evidence from more invasive techniques, such as anatomical tracing studies and electrophysiological investigations only possible in nonhuman species.

Functional brain changes underlying irritability in premanifest Huntington's disease.

The clinical phenotype of Huntington's disease (HD) consists of motor, cognitive and psychiatric symptoms, of which irritability is an important manifestation. Our aim was to identify the functional and structural brain changes that underlie irritability in premanifest HD (preHD). Twenty preHD carriers and 20 gene-negative controls from HD families took part in the study. Although the 5-year probability of disease onset was only 11%, the preHD group showed striatal atrophy and increased clinical irritability ratings. Functional MRI was performed during a mood induction experiment by means of recollection of emotional (angry, sad, and happy) and neutral autobiographical episodes. While there were no significant group differences in the subjective intensity of the emotional experience, the preHD group showed increased anger-selective activation in a distributed network, including the pulvinar, cingulate cortex, and somatosensory association cortex, compared to gene-negative controls. Pulvinar activation during anger experience correlated negatively with putaminal grey matter volume and positively with irritability ratings in the preHD group. In addition, the preHD group showed a decrease in anger-selective activation in the amygdala, which correlated with putaminal and caudate grey matter volume. In conclusion, compared to gene-negative controls, anger experience in preHD is associated with activity changes in a distributed set of regions known to be involved in emotion regulation. Increased activity is related to behavioral and volumetric measures, providing insight in the pathophysiology of early neuropsychiatric symptoms in preHD.

Neural correlates of visual motion processing without awareness in patients with striate cortex and pulvinar lesions.

Patients with striate cortex lesions experience visual perception loss in the contralateral visual field. In few patients, however, stimuli within the blind field can lead to unconscious (blindsight) or even conscious perception when the stimuli are moving (Riddoch syndrome). Using functional magnetic resonance imaging (fMRI), we investigated the neural responses elicited by motion stimulation in the sighted and blind visual fields of eight patients with lesions of the striate cortex. Importantly, repeated testing ensured that none of the patients exhibited blindsight or a Riddoch syndrome. Three patients had additional lesions in the ipsilesional pulvinar. For blind visual field stimulation, great care was given that the moving stimulus was precisely presented within the borders of the scotoma. In six of eight patients, the stimulation within the scotoma elicited hemodynamic activity in area human middle temporal (hMT) while no activity was observed within the ipsilateral lesioned area of the striate cortex. One of the two patients in whom no ipsilesional activity was observed had an extensive lesion including massive subcortical damage. The other patient had an additional focal lesion within the lateral inferior pulvinar. Fiber-tracking based on anatomical and functional markers (hMT and Pulvinar) on individual diffusion tensor imaging (DTI) data from each patient revealed the structural integrity of subcortical pathways in all but the patient with the extensive subcortical lesion. These results provide clear evidence for the robustness of direct subcortical pathways from the pulvinar to area hMT in patients with striate cortex lesions and demonstrate that ipsilesional activity in area hMT is completely independent of conscious perception.

Altered network connectivity in frontotemporal dementia with C9orf72 hexanucleotide repeat expansion.

Hexanucleotide repeat expansion in C9orf72 represents the most common genetic cause of familial and sporadic behavioural variant frontotemporal dementia. Previous studies show that some C9orf72 carriers with behavioural variant frontotemporal dementia exhibit distinctive atrophy patterns whereas others show mild or undetectable atrophy despite severe behavioural impairment. To explore this observation, we examined intrinsic connectivity network integrity in patients with or without the C9orf72 expansion. We studied 28 patients with behavioural variant frontotemporal dementia, including 14 C9orf72 mutation carriers (age 58.3 ± 7.7 years, four females) and 14 non-carriers (age 60.8 ± 6.9 years, four females), and 14 age- and sex-matched healthy controls. Both patient groups included five patients with comorbid motor neuron disease. Neuropsychological data, structural brain magnetic resonance imaging, and task-free functional magnetic resonance imaging were obtained. Voxel-based morphometry delineated atrophy patterns, and seed-based intrinsic connectivity analyses enabled group comparisons of the salience, sensorimotor, and default mode networks. Single-patient analyses were used to explore network imaging as a potential biomarker. Despite contrasting atrophy patterns in C9orf72 carriers versus non-carriers, patient groups showed topographically similar connectivity reductions in the salience and sensorimotor networks. Patients without C9orf72 expansions exhibited increases in default mode network connectivity compared to controls and mutation carriers. Across all patients, behavioural symptom severity correlated with diminished salience network connectivity and heightened default mode network connectivity. In C9orf72 carriers, salience network connectivity reduction correlated with atrophy in the left medial pulvinar thalamic nucleus, and this region further showed diminished connectivity with key salience network hubs. Single-patient analyses revealed salience network disruption and default mode network connectivity enhancement in C9orf72 carriers with early-stage or slowly progressive symptoms. The findings suggest that patients with behavioural variant frontotemporal dementia with or without the C9orf72 expansion show convergent large-scale network breakdowns despite distinctive atrophy patterns. Medial pulvinar degeneration may contribute to the behavioural variant frontotemporal dementia syndrome in C9orf72 carriers by disrupting salience network connectivity. Task-free functional magnetic resonance imaging shows promise in detecting early-stage disease in C9orf72 carriers and may provide a unifying biomarker across diverse anatomical variants.

From affective blindsight to emotional consciousness.

Following destruction or denervation of the primary visual cortex (V1) cortical blindness ensues. Affective blindsight refers to the uncanny ability of such patients to respond correctly, or above chance level, to visual emotional expressions presented to their blind fields. Fifteen years after its original discovery, affective blindsight still fascinates neuroscientists and philosophers alike, as it offers a unique window on the vestigial properties of our visual system that, though present in the intact brain, tend to be unnoticed or even actively inhibited by conscious processes. Here we review available studies on affective blindsight with the intent to clarify its functional properties, neural bases and theoretical implications. Evidence converges on the role of subcortical structures of old evolutionary origin such as the superior colliculus, the pulvinar and the amygdala in mediating affective blindsight and nonconscious perception of emotions. We conclude that approaching consciousness, and its absence, from the vantage point of emotion processing may uncover important relations between the two phenomena, as consciousness may have evolved as an evolutionary specialization to interact with others and become aware of their social and emotional expressions.

Evidence of diagnostic specificity in the neural correlates of facial affect processing in bipolar disorder and schizophrenia: a meta-analysis of functional imaging studies.

BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) may overlap in etiology and phenomenology but differ with regard to emotional processing. We used facial affect as a probe for emotional processing to determine whether there are diagnosis-related differences between SZ and BD in the function of the underlying neural circuitry. METHOD: Functional magnetic resonance imaging (fMRI) studies published up to 30 April 2012 investigating facial affect processing in patients with SZ or BD were identified through computerized and manual literature searches. Activation foci from 29 studies encompassing 483 healthy individuals, 268 patients with SZ and 267 patients with BD were subjected to voxel-based quantitative meta-analysis using activation likelihood estimation (ALE). RESULTS: Compared to healthy individuals, when emotional facial stimuli were contrasted to neutral stimuli, patients with BD showed overactivation within the parahippocampus/amygdala and thalamus and reduced engagement within the ventrolateral prefrontal cortex (PFC) whereas patients with SZ showed underactivation throughout the entire facial affect processing network and increased activation in visual processing regions within the cuneus. Patients with BD showed greater thalamic engagement compared to patients with SZ; in the reverse comparison, patients with SZ showed greater engagement in posterior associative visual cortices. CONCLUSIONS: During facial affect processing, patients with BD show overactivation in subcortical regions and underactivation in prefrontal regions of the facial affect processing network, consistent with the notion of reduced emotional regulation. By contrast, overactivation within visual processing regions coupled with reduced engagement of facial affect processing regions points to abnormal visual integration as the core underlying deficit in SZ.

[Pulvinar]. / Pulvinar.

The pulvinar is the largest nucleus of the thalamus. Its lateral and inferior areas have rich connections with the visual- and dorsolateral parietal cortices. Several cells in the medial and upper area connect the anterior cingulum and the premotor and prefrontal association areas. This neuronal network was considered to organize the saccades and visual attention. Other cells in the medial nucleus have axonal connections with paralimbic-, insular and higher order association-cortices. The medial structure integrates complex sensory information with limbic reactivity settings, transmitting these to the temporal and parieto-occipital centres. The pulvinar is supplied by the posterior chorioideal artery. Visual salience is considered to be an important function of the pulvinar. Visual selection enables subjects to choose the actually adequate behavioral act. To serve the visual salience the pulvinar may also inhibit inappropriate eye movements. The pulvinar appears to be a key structure of the EEG's alpha rhythm generator, acting together with the parietooccipital and temporal cortices. Dynamic fluctuation of BOLD signals on fMRI correlates well with the change of alpha power even in resting state. We presume that the pulvinar is part of a closed cortico-subcortical circuit, analogous with the striatum, but the output of the pulvinar initiates complex behavioral reactions, including perception, selective attention and emotions. Damage of the pulvinar may elicit contralateral visual neglect, because of the dissociation of the neuronal network integrated by the superior temporal area. Increased activity of the pulvinar was found during abrupt reaction to fearful visual signals; and also in the etiopathology of endogenous depressions through the alteration of serotonin transporters. Increased bilateral signal intensity of the pulvinar on MRI was detected in cases of the new variants of Creutzfeldt-Jakob- and Fabry diseases.

Impaired attentional selection following lesions to human pulvinar: evidence for homology between human and monkey.

We examined the contributions of the human pulvinar to goal directed selection of visual targets in 3 patients with chronic, unilateral lesions involving topographic maps in the ventral pulvinar. Observers completed 2 psychophysical tasks in which they discriminated the orientation of a lateralized target grating in the presence of vertically-aligned distracters. In experiment 1, where distracter contrast was varied while target contrast remained constant, the patients' contralesional contrast thresholds for discriminating the orientation of grating stimuli were elevated only when the task required selection of a visual target in the face of competition from a salient distracter. Attentional selectivity was restored in the patients in experiment 2 where target contrast was varied while distracter contrast remained constant. These observations provide the first evidence that the human pulvinar plays a necessary role in modulating physical saliency in attentional selection, and supports a homology in global pulvinar structure between humans and monkey.

Resting-State Functional Connectivity of the Thalamus in Complete Spinal Cord Injury.

Background. Neuroimaging studies of spinal cord injury (SCI) have mostly examined the functional organization of the cortex, with only limited focus on the subcortical substrates of the injury. However, thalamus is an important modulator and sensory relay that requires investigation at a subnuclei level to gain insight into the neuroplasticity following SCI. Objective. To use resting-state functional magnetic resonance imaging to examine the functional connectivity (FC) of thalamic subnuclei in complete SCI patients. Methods. A seed-based connectivity analysis was applied for 3 thalamic subnuclei: pulvinar, mediodorsal, and ventrolateral nucleus in each hemisphere. A nonparametric 2-sample t test with permutations was applied for each of the 6 thalamic seeds to compute FC differences between 22 healthy controls and 19 complete SCI patients with paraplegia. Results. Connectivity analysis showed a decrease in the FC of the bilateral mediodorsal nucleus with right superior temporal gyrus and anterior cingulate cortex in the SCI group. Similarly, the left ventrolateral nucleus exhibited decreased FC with left superior temporal gyrus in SCI group. In contrast, left pulvinar nucleus demonstrated an increase in FC with left inferior frontal gyrus and left inferior parietal lobule in SCI group. Our findings also indicate a negative relationship between postinjury durations and thalamic FC to regions of sensorimotor and visual cortices, where longer postinjury durations (~12 months) is associated with higher negative connectivity between these regions. Conclusion. This study provides evidence for reorganization in the thalamocortical connections known to be involved in multisensory integration and affective processing, with possible implications in the generation of sensory abnormalities after SCI.

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.

Blue light activates pulvinar nuclei in longstanding idiopathic photophobia: A case report.

Numerous pathologies can contribute to photophobia. When considering light transduction alone, photophobia may be triggered through melanopsin pathways (non-image forming), rod and cone pathways (image-forming), or some combination of the two. We evaluated a 39 year old female patient with longstanding idiopathic photophobia that was exacerbated by blue light, and tested her by presenting visual stimuli in an event-related fMRI experiment. Analysis showed significantly greater activation in bilateral pulvinar nuclei, associated with the melanopsin intrinsically photosensitive retinal ganglion cell (ipRGC) visual pathway, and their activation is consistent with the patient's report that blue light differentially evoked photophobia. This appears to be the first demonstration of functional activation of the ipRGC pathway during photophobia in a patient.