A multimodal interface for speech perception: the role of the left superior temporal sulcus in social cognition and autism.

Multimodal integration is crucial for human interaction, in particular for social communication, which relies on integrating information from various sensory modalities. Recently a third visual pathway specialized in social perception was proposed, which includes the right superior temporal sulcus (STS) playing a key role in processing socially relevant cues and high-level social perception. Importantly, it has also recently been proposed that the left STS contributes to audiovisual integration of speech processing. In this article, we propose that brain areas along the right STS that support multimodal integration for social perception and cognition can be considered homologs to those in the left, language-dominant hemisphere, sustaining multimodal integration of speech and semantic concepts fundamental for social communication. Emphasizing the significance of the left STS in multimodal integration and associated processes such as multimodal attention to socially relevant stimuli, we underscore its potential relevance in comprehending neurodevelopmental conditions characterized by challenges in social communication such as autism spectrum disorder (ASD). Further research into this left lateral processing stream holds the promise of enhancing our understanding of social communication in both typical development and ASD, which may lead to more effective interventions that could improve the quality of life for individuals with atypical neurodevelopment.

The functional connectivity of the right superior temporal gyrus is associated with psychological risk and resilience factors for suicidality.

INTRODUCTION: Suicide attempters show increased activation in the right superior temporal gyrus (rSTG). Here, we investigated the rSTG functional connectivity (FC) to identify a functional network involved in suicidality and its associations with psychological suicidality risk and resilience factors. METHODS: The resting state functional magnetic resonance imaging data of 151 healthy individuals from the Human Connectome Project Young Adult database were used to explore the FC of the rSTG with itself and with the rest of the brain. The correlation between the rSTG FC and loneliness and purpose in life scores was assessed with the NIH Toolbox. The effect of sex was also investigated. RESULTS: The rSTG had a positive FC with bilateral cortical and subcortical regions, including frontal, temporal, parietal, occipital, limbic, and cerebellar regions, and a negative FC with the medulla oblongata. The FC of the rSTG with itself and with the left central operculum were associated with loneliness scores. The within rSTG FC was also negatively correlated with purpose in life scores, although at a trend level. We did not find any effect of sex on FC and its associations with psychological factors. LIMITATIONS: The cross-sectional design, the limited age range, and the lack of measures of suicidality limit the generalizability of our findings. CONCLUSIONS: The rSTG functional network is associated with loneliness and purpose in life. Together with the existing literature on suicide, this supports the idea that the neural activity of rSTG may contribute to suicidality by modulating risk and resilience factors associated with suicidality.

Radiological correlates of pseudobulbar affect: Corticobulbar and cerebellar components in primary lateral sclerosis.

INTRODUCTION: Pseudobulbar affect (PBA) is a distressing symptom of a multitude of neurological conditions affecting patients with a rage of neuroinflammatory, neurovascular and neurodegenerative conditions. It manifests in disproportionate emotional responses to minimal or no contextual stimulus. It has considerable quality of life implications and treatment can be challenging. METHODS: A prospective multimodal neuroimaging study was conducted to explore the neuroanatomical underpinnings of PBA in patients with primary lateral sclerosis (PLS). All participants underwent whole genome sequencing and screening for C9orf72 hexanucleotide repeat expansions, a comprehensive neurological assessment, neuropsychological screening (ECAS, HADS, FrSBe) and PBA was evaluated by the emotional lability questionnaire. Structural, diffusivity and functional MRI data were systematically evaluated in whole-brain (WB) data-driven and region of interest (ROI) hypothesis-driven analyses. In ROI analyses, functional and structural corticobulbar connectivity and cerebello-medullary connectivity alterations were evaluated separately. RESULTS: Our data-driven whole-brain analyses revealed associations between PBA and white matter degeneration in descending corticobulbar as well as in commissural tracts. In our hypothesis-driven analyses, PBA was associated with increased right corticobulbar tract RD (p = 0.006) and decreased FA (p = 0.026). The left-hemispheric corticobulbar tract, as well as functional connectivity, showed similar tendencies. While uncorrected p-maps revealed both voxelwise and ROI trends for associations between PBA and cerebellar measures, these did not reach significance to unequivocally support the "cerebellar hypothesis". CONCLUSIONS: Our data confirm associations between cortex-brainstem disconnection and the clinical severity of PBA. While our findings may be disease-specific, they are consistent with the classical cortico-medullary model of pseudobulbar affect.

Source space connectomics of neurodegeneration: One-metric approach does not fit all.

Brain functional connectivity in dementia has been assessed with dissimilar EEG connectivity metrics and estimation procedures, thereby increasing results' heterogeneity. In this scenario, joint analyses integrating information from different metrics may allow for a more comprehensive characterization of brain functional interactions in different dementia subtypes. To test this hypothesis, resting-state electroencephalogram (rsEEG) was recorded in individuals with Alzheimer's Disease (AD), behavioral variant frontotemporal dementia (bvFTD), and healthy controls (HCs). Whole-brain functional connectivity was estimated in the EEG source space using 101 different types of functional connectivity, capturing linear and nonlinear interactions in both time and frequency-domains. Multivariate machine learning and progressive feature elimination was run to discriminate AD from HCs, and bvFTD from HCs, based on joint analyses of i) EEG frequency bands, ii) complementary frequency-domain metrics (e.g., instantaneous, lagged, and total connectivity), and iii) time-domain metrics with different linearity assumption (e.g., Pearson correlation coefficient and mutual information). <10% of all possible connections were responsible for the differences between patients and controls, and atypical connectivity was never captured by >1/4 of all possible connectivity measures. Joint analyses revealed patterns of hypoconnectivity (patientsHCs) in both groups was mainly identified in frontotemporal regions. These atypicalities were differently captured by frequency- and time-domain connectivity metrics, in a bandwidth-specific fashion. The multi-metric representation of source space whole-brain functional connectivity evidenced the inadequacy of single-metric approaches, and resulted in a valid alternative for the selection problem in EEG connectivity. These joint analyses reveal patterns of brain functional interdependence that are overlooked with single metrics approaches, contributing to a more reliable and interpretable description of atypical functional connectivity in neurodegeneration.

Intracerebral electrical stimulation of the right anterior fusiform gyrus impairs human face identity recognition.

Brain regions located between the right fusiform face area (FFA) in the middle fusiform gyrus and the temporal pole may play a critical role in human face identity recognition but their investigation is limited by a large signal drop-out in functional magnetic resonance imaging (fMRI). Here we report an original case who is suddenly unable to recognize the identity of faces when electrically stimulated on a focal location inside this intermediate region of the right anterior fusiform gyrus. The reliable transient identity recognition deficit occurs without any change of percept, even during nonverbal face tasks (i.e., pointing out the famous face picture among three options; matching pictures of unfamiliar or familiar faces for their identities), and without difficulty at recognizing visual objects or famous written names. The effective contact is associated with the largest frequency-tagged electrophysiological signals of face-selectivity and of familiar and unfamiliar face identity recognition. This extensive multimodal investigation points to the right anterior fusiform gyrus as a critical hub of the human cortical face network, between posterior ventral occipito-temporal face-selective regions directly connected to low-level visual cortex, the medial temporal lobe involved in generic memory encoding, and ventral anterior temporal lobe regions holding semantic associations to people's identity.

The Auditory Afferent Pathway as a Clinical Marker of Alzheimer's Disease.

Brain stem neural tracts and nuclei may be disturbed prior to observable neuronal atrophy in AD. In this perspective, we discuss the notion of functional deficits presenting prior to structural abnormalities in Alzheimer's disease (AD). Imaging of inferior colliculi using magnetic resonance spectroscopy (MRS) shows significant decrease in the neuronal markers, N acetyl aspartate/creatine ratio and increase in the glial marker myo-Inositol, in subjects with Mini-Mental State Examination scores greater than 24 and with no signs of atrophy in their MRI of the medial temporal lobe. Abnormalities in components of the auditory event-related potentials (ERPs) are described in cognitive impairment including AD. We observed a significant decrease in amplitude and increase in latency during the first 10 ms of auditory evoked potentials measured on electroencephalography (EEG) indicating slow auditory response of the brainstem. EEG spectral power recorded at the cortex is also associated with neural activity at the level of the inferior colliculi. We postulate that a functional examination of auditory afferent pathways, using non-invasive techniques, such as MRS, brain stem auditory evoked potentials (BAEPs) and ERPs may improve diagnostic accuracy of AD. Functional changes precede structural changes and it is important to further understand the relationship between biochemical and electrophysiological measures such as MRS, BAEPs and EEG.

Relationship between location of epileptic focus and occurrence during sleep versus wakefulness.

Different sleep stages exert differential effects on interictal discharges, neural synchrony and seizure threshold. We sought to assess the relationship between localization of the epileptogenic focus and seizure distribution in sleep versus wakefulness among patients with refractory epilepsy. We conducted a retrospective chart review-based study. Video-electroencephalography of patients with refractory epilepsy, planned for resective surgery, were reviewed for seizure localisation and occurrence relative to stage of sleep/wakefulness. Demographic/clinical data, including details of surgery, were also recorded. Bivariate analysis was conducted using the chi-square test for proportions and unpaired t-test/ANOVA to compare the means within groups. We enrolled 175 patients (107 males) with a mean age of 26.1 + 9.8 years (range: 4-53 years). We analysed 1,282 seizures, of which 916 (71.5%) were temporal, 95 (7.4%) frontal, 144 (11.2 %) central/ parietal and 19 (1.5%) arose from the occipital lobe. Temporal lobe onset seizures were more frequent during wakefulness (77.7%) compared to extra-temporal localization (65%) (p<0.0001). Amongst temporal lobe onset seizures, those during wakefulness arose more frequently from the lateral temporal (88.6%) compared to the mesial temporal lobe (75.5%) (p=0.0003). A higher proportion of seizures evolved into secondary generalisation during sleep (23.5%) versus 8.7% during wakefulness (p<0.0001). Our study demonstrates that lobar location of epileptogenic foci is associated with a predilection of seizures to occur, as well as secondarily generalise, during sleep/wakefulness. Seizures with lateral temporal lobe as well as extratemporal lobe onset were more likely to occur during wakefulness. Overall, sleep related seizures were more likely to be of extratemporal lobe onset, though.

Pros and cons in tinnitus brain: Enhancement of global connectivity for alpha and delta waves.

Interactions among cortical areas of tinnitus brain remained unclear. Weaker alpha and stronger delta activities in tinnitus have been noted over auditory cortices. However, the interplay between a single substrate with whole brain within alpha/delta band remained unknown. Thirty-one patients with chronic tinnitus were recruited. Thirty-four healthy volunteers served as controls. Magnetoencephalographic measurements of spontaneous activities were performed. The strength of alpha/delta activities was analyzed. By dividing cortices into 38 regions of interest (ROIs), measurements of connectivity were performed using amplitude envelope correlation (AEC). Global connectivity was calculated by adding and averaging connectivity of single ROI with every other region. There were no significant differences in mean power of alpha and delta band between groups, despite the trend of stronger alpha and weaker delta band in controls. The global connectivity of alpha wave was significantly stronger in tinnitus for left frontal pole, and of delta wave for bilateral pars orbitalis, bilateral superior temporal, bilateral middle temporal, right pars triangularis, right transverse temporal, right inferior temporal, and right supra-marginal. The global connectivity of alpha/delta waves was enhanced for tinnitus in designated ROIs of frontal/temporal/parietal lobes. The underlying mechanism(s) might be associated with augmentation/modulation of tinnitus perception. Our results corroborated the evolving consensus about neural correlates inside frontal/temporal/parietal lobes as essential elements of hubs for central processing of tinnitus. Further study to explore the resolution of effective connectivity between those ROIs and respective substrates by using AEC will be necessary for the evaluation of pathogenetic scenario for tinnitus.

Cascade process mediated by left hippocampus and left superior frontal gyrus affects relationship between aging and cognitive dysfunction.

BACKGROUND: Cognitive function declines with age and has been shown to be associated with atrophy in some brain regions, including the prefrontal cortex. However, the details of the relationship between aging and cognitive dysfunction are not well understood. METHODS: Across a wide range of ages (24- to 85-years-old), this research measured the gray matter volume of structural magnetic resonance imaging data in 39 participants, while some brain regions were set as mediator variables to assess the cascade process between aging and cognitive dysfunction in a path analysis. RESULTS: Path analysis showed that age affected the left hippocampus, thereby directly affecting the left superior frontal gyrus. Furthermore, the gyrus directly affected higher order flexibility and maintenance abilities calculated as in the Wisconsin card sorting test, and the two abilities affected the assessment of general cognitive function. CONCLUSION: Our finding suggests that a cascade process mediated by the left hippocampus and left superior frontal gyrus is involved in the relationship between aging and cognitive dysfunction.

Functional alterations in cortical processing of speech in glioma-infiltrated cortex.

Recent developments in the biology of malignant gliomas have demonstrated that glioma cells interact with neurons through both paracrine signaling and electrochemical synapses. Glioma-neuron interactions consequently modulate the excitability of local neuronal circuits, and it is unclear the extent to which glioma-infiltrated cortex can meaningfully participate in neural computations. For example, gliomas may result in a local disorganization of activity that impedes the transient synchronization of neural oscillations. Alternatively, glioma-infiltrated cortex may retain the ability to engage in synchronized activity in a manner similar to normal-appearing cortex but exhibit other altered spatiotemporal patterns of activity with subsequent impact on cognitive processing. Here, we use subdural electrocorticography to sample both normal-appearing and glioma-infiltrated cortex during speech. We find that glioma-infiltrated cortex engages in synchronous activity during task performance in a manner similar to normal-appearing cortex but recruits a diffuse spatial network. On a temporal scale, we show that signals from glioma-infiltrated cortex have decreased entropy, which may affect its ability to encode information during nuanced tasks such as production of monosyllabic versus polysyllabic words. Furthermore, we show that temporal decoding strategies for distinguishing monosyllabic from polysyllabic words were feasible for signals arising from normal-appearing cortex but not from glioma-infiltrated cortex. These findings inform our understanding of cognitive processing in chronic disease states and have implications for neuromodulation and prosthetics in patients with malignant gliomas.

Changes in the language system as amyloid-ß accumulates.

Language dysfunction is common in Alzheimer's disease. There is increasing interest in the preclinical or asymptomatic phase of Alzheimer's disease. Here we examined in 35 cognitively intact older adults (age range 52-78 years at baseline, 17 male) in a longitudinal study design the association between accumulation of amyloid over a 5-6-year period, measured using PET, and functional changes in the language network measured over the same time period using task-related functional MRI. In the same participants, we also determined the association between the longitudinal functional MRI changes and a cross-sectional measure of tau load as measured with 18F-AV1451 PET. As predicted, the principal change occurred in posterior temporal cortex. In the cortex surrounding the right superior temporal sulcus, the response amplitude during the associative-semantic versus visuo-perceptual task increased over time as amyloid load accumulated (Pcorrected = 0.008). In a whole-brain voxel-wise analysis, amyloid accumulation was also associated with a decrease in response amplitude in the left inferior frontal sulcus (Pcorrected = 0.009) and the right dorsomedial prefrontal cortex (Pcorrected = 0.005). In cognitively intact older adults, cross-sectional tau load was not associated with longitudinal changes in functional MRI response amplitude. Our findings confirm the central role of the neocortex surrounding the posterior superior temporal sulcus as the area of predilection within the language network in the earliest stages of Alzheimer's disease. Amyloid accumulation has an impact on cognitive brain circuitry in the asymptomatic phase of Alzheimer's disease.

Temporo-cerebellar connectivity underlies timing constraints in audition.

The flexible and efficient adaptation to dynamic, rapid changes in the auditory environment likely involves generating and updating of internal models. Such models arguably exploit connections between the neocortex and the cerebellum, supporting proactive adaptation. Here, we tested whether temporo-cerebellar disconnection is associated with the processing of sound at short timescales. First, we identify lesion-specific deficits for the encoding of short timescale spectro-temporal non-speech and speech properties in patients with left posterior temporal cortex stroke. Second, using lesion-guided probabilistic tractography in healthy participants, we revealed bidirectional temporo-cerebellar connectivity with cerebellar dentate nuclei and crura I/II. These findings support the view that the encoding and modeling of rapidly modulated auditory spectro-temporal properties can rely on a temporo-cerebellar interface. We discuss these findings in view of the conjecture that proactive adaptation to a dynamic environment via internal models is a generalizable principle.

Temporal lobe activation during episodic memory encoding following traumatic brain injury.

The temporal lobes are critical for encoding and retrieving episodic memories. The temporal lobes are preferentially disrupted following a traumatic brain injury (TBI), likely contributing to the difficulties observed in episodic memory. However, the underlying neural changes that precipitate or maintain these difficulties in individuals with TBI remains poorly understood. Here, we use functional magnetic resonance imaging (fMRI) to interrogate the relationship between temporal lobe activation and encoding of episodic stimuli. Participants encoded face, scene, and animal stimuli during an fMRI run. In an out-of-scanner task, participants were required to correctly identify previously displayed stimuli over two presentation runs (each in-scanner stimuli presented twice). Forty-three patients with moderate-severe TBI were recruited and compared with 38 demographically similar healthy controls. The pattern of behavioural performance between groups depended on the stimuli presentation run. The TBI group demonstrated poorer episodic memory for faces and scenes during the first presentation, but not the second presentation. When episodic memory was analysed across all presentation runs, behavioural deficits were only apparent for faces. Interestingly, processing of faces emerged as the only between group-difference on fMRI, whereby TBI participants had an increased signal in the middle temporal gyrus extending to the superior temporal sulcus. These findings provide evidence to suggest that following TBI: (a) episodic memory is preferentially impaired for complex stimuli such as faces, and (b) robust behavioural inefficiencies are reflected in increased activation in specific temporal lobe structures during encoding.

Contrasting dorsal caudate functional connectivity patterns between frontal and temporal cortex with BMI increase: link to cognitive flexibility.

BACKGROUND: Obesity is associated with brain intrinsic functional reorganization. However, little is known about the BMI-related interhemispheric functional connectivity (IHFC) alterations, and their link with executive function in young healthy adults. METHODS: We examined voxel-mirrored homotopic connectivity (VMHC) patterns in 417 young adults from the Human Connectome Project. Brain regions with significant association between BMI and VMHC were identified using multiple linear regression. Results from these analyses were then used to determine regions for seed-voxel FC analysis, and multiple linear regression was used to explore the brain regions showing significant association between BMI and FC. The correlations between BMI-related executive function measurements and VMHC, as well as seed-voxel FC, were further examined. RESULTS: BMI was negatively associated with scores of Dimensional Change Card Sort Test (DCST) assessing cognitive flexibility (r = -0.14, p = 0.006) and with VMHC of bilateral inferior parietal lobule, insula and dorsal caudate. The dorsal caudate emerged as a nexus for BMI-related findings: greater BMI was associated with greater FC between caudate and hippocampus and lower FC between caudate and several prefrontal nodes (right inferior frontal gyrus, anterior cingulate cortex, and middle frontal gyrus). The FC between right caudate and left hippocampus was negatively associated with scores of DCST (r = -0.15, p = 0.0018). CONCLUSIONS: Higher BMI is associated with poorer cognitive flexibility performance and IHFC in an extensive set of brain regions implicated in cognitive control. Larger BMI was associated with higher caudate-medial temporal lobe FC and lower caudate-dorsolateral prefrontal cortex FC. These findings may have relevance for executive function associated with weight gain among otherwise healthy young adults.

Delta band activity contributes to the identification of command following in disorder of consciousness.

The overt or covert ability to follow commands in patients with disorders of consciousness is considered a sign of awareness and has recently been defined as cortically mediated behaviour. Despite its clinical relevance, the brain signatures of the perceptual processing supporting command following have been elusive. This multimodal study investigates the temporal spectral pattern of electrical brain activity to identify features that differentiated healthy controls from patients both able and unable to follow commands. We combined evidence from behavioural assessment, functional neuroimaging during mental imagery and high-density electroencephalography collected during auditory prediction, from 21 patients and 10 controls. We used a penalised regression model to identify command following using features from electroencephalography. We identified seven well-defined spatiotemporal signatures in the delta, theta and alpha bands that together contribute to identify DoC subjects with and without the ability to follow command, and further distinguished these groups of patients from controls. A fine-grained analysis of these seven signatures enabled us to determine that increased delta modulation at the frontal sensors was the main feature in command following patients. In contrast, higher frequency theta and alpha modulations differentiated controls from both groups of patients. Our findings highlight a key role of spatiotemporally specific delta modulation in supporting cortically mediated behaviour including the ability to follow command. However, patients able to follow commands nevertheless have marked differences in brain activity in comparison with healthy volunteers.

Neural networks associated with quality of life in patients with Parkinson's disease.

INTRODUCTION: The neural underpinnings of health-related quality of life in Parkinson's disease remain unclear. This study was conducted to unravel which motor and non-motor symptoms in Parkinson's disease influence health-related quality of life and reveal neural networks most likely linked to it. METHODS: Comprehensive clinical assessments were conducted for 247 Parkinson's disease patients and image analyses were performed for 181 patients. Clinical scores commonly used to assess various symptoms related to health-related quality of life were investigated. Factor and resting-state functional magnetic resonance imaging analyses were reviewed to reveal health-related quality of life-associated brain networks. RESULTS: The Spearman's rank correlation coefficient for the Parkinson's disease Questionnaire-39 summary index was high in the Activities-specific Balance Confidence Scale, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 2, Freezing of Gait Questionnaire, and Self-reported Autonomic Symptoms in Parkinson's disease. Multiple regression and Random Forest regression analyses indicated that health-related quality of life-associated factors were Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part 1, Depression Rating Scales, and the above-mentioned scales. The resting-state functional magnetic resonance imaging analysis revealed decreased functional connectivity between the anterior cingulate cortex and right temporo-parietal junction as health-related quality of life worsened. CONCLUSION: Fear of falling, daily living activities, gait freezing, and autonomic dysfunction have notable effects on health-related quality of life in Parkinson's disease. Brain networks consisting of the anterior cingulate cortex and temporo-parietal junction may be associated with the emotion-related and social factors of health-related quality of life in Parkinson's disease.

Interrelations of Cerebral Hemodynamics with Parameters of Cardiac Function and Brain Tissue in Patients with Ischemic Stroke.

We analyzed interrelations between the cerebral blood flow, cardiac output, and condition of the brain substance in 530 patients with ischemic stroke. Dependencies between the linear blood flow velocities in all arteries supplying the brain, as well as between the total volume blood flow through the internal carotid arteries and left ventricular stroke volume were revealed. The severity of atrophy was maximum in the parietal lobes (median 1.5 (1.0; 2.0)) and minimum in the occipital lobes (median 0.5 (0; 1.0)). Temporal lobes cortical atrophy significantly correlated with changes in the limbic system and in the periventricular and deep white matter; a significant weak inverse correlation of this parameter with blood flow in the middle cerebral artery was also found. Changes in the periventricular white matter (but not in deep white matter) demonstrated a significant inverse correlation with blood flow in the middle and anterior cerebral arteries.

Functional stability predicts depressive and cognitive improvement in major depressive disorder: A longitudinal functional MRI study.

Functional stability is a newly developed dynamic functional connectivity approach. The objective of this study was to adopt functional stability to investigate diagnosis-associated abnormalities (patients vs. controls) and status-related changes (acute vs. remitted status) in brain function in major depressive disorder (MDD). 132 MDD patients and 102 healthy controls underwent resting-state functional MRI as well as clinical and cognitive assessment at baseline, with 48 patients completing follow-up examinations at an average of 7 months. Results showed no group differences in baseline functional stability and no longitudinal functional stability changes from acute to remitted status in patients. However, we found that baseline functional stability in the dorsal and ventral anterior cingulate cortex, calcarine sulcus, and middle occipital gyrus could predict improvement in depressive symptoms from acute to remitted status in MDD patients, with longitudinal functional stability changes in these regions related to the degree of symptom improvement. In addition, lower baseline functional stability in the inferior temporal gyrus could predict a greater improvement in sustained attention, which was associated with a greater functional stability increase in this region. Our findings highlight functional stability as a potential prognostic biomarker to predict and track disease progression or stratify MDD patients for optimizing disease management and treatment strategies.

Differential regulation of excitatory synaptic transmission in the hippocampus and anterior temporal lobe by cyclin dependent kinase 5 (Cdk5) in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS).

Mesial temporal lobe epilepsy with hippocamapal sclerosis (MTLE-HS) is the most common form of drug resistant epilepsy (DRE). MTLE-HS is a distributed network disorder comprising of not only the hippocampus, but other anatomically related extrahippocampal regions. Excitatory synaptic transmission is differentially regulated in the hippocampal and extra-hippocampal regions of patients with MTLE-HS, but its mechanism not understood. Cyclin-dependent kinase 5 (Cdk5) is known to regulate synaptic transmission and plasticity through up-regulation of NMDA receptors by phosphorylating NR2Asubunits. The present study is designed to investigate whether Cdk5 differentially regulates the excitatory synaptic transmission in the hippocampus and anterior temporal lobe (ATL) samples obtained from patients of MTLE-HS. We have measured the Cdk5 kinase activity and the protein levels of Cdk5, p-Cdk5, p35/p25, NR2A, pNR2A in the hippocampal and ATL samples obtained from patients with MTLE-HS. We have also determined the effect of roscovitine, a Cdk5 antagonist, on spontaneous excitatory postsynaptic currents (EPSCs) recorded from the hippocampal and ATL using patch-clamp technique. We observed significant increase in the expression of Cdk5, p-Cdk5, p35/p25, NR2A, pNR2A in the ATL samples as compared to the hippocampal samples. Cdk5 activity was significantly higher in ATL samples as compared to the hippocampal samples. Magnitude of reduction in the frequency of EPSCs by roscovitine in the ATL samples was higher than that in the hippocampal samples. Our studies suggest that Cdk5 differentially regulates excitatory synaptic activity in the hippocampal and ATL region of patients with MTLE-HS.

Highly consistent temporal lobe interictal spike networks revealed from foramen ovale electrodes.

OBJECTIVE: A major challenge that limits understanding and treatment of epileptic events from mesial temporal structures comes from our inability to detect and map interictal networks reproducibly using scalp electrodes. Here, we developed a novel approach to map interictal spike networks and demonstrate their relationships to seizure onset and lesions in patients with foramen ovale electrode implantations. METHODS: We applied the direct Directed Transfer Function to reveal interictal spike propagation from bilateral foramen ovale electrodes on 10 consecutive patients and co-registered spatially with both seizure onset zones and temporal lobe lesions. RESULTS: Highly reproducible, yet unique interictal spike networks were seen for each patient (correlation: 0.93 ±â€¯0.13). Interictal spikes spread in both anterior and posterior directions within each temporal lobe, often reverberating between sites. Spikes propagated to the opposite temporal lobe predominantly through posterior pathways. Patients with structural lesions (N = 4), including tumors and sclerosis, developed reproducible spike networks adjacent to their lesions that were highly lateralized compared to patients without lesions. Only 5% of mesial temporal lobe spikes were time-locked with scalp electrode spikes. Our preliminary observation on two lesional patients suggested that along with lesion location, Interictal spike networks also partially co-registered with seizure onset zones suggesting interrelationship between seizure onset and a subset of spike networks. CONCLUSIONS: This is the first demonstration of patient-specific, reproducible interictal spike networks in mesial temporal structures that are closely linked to both temporal lobe lesions and seizure onset zones. SIGNIFICANCE: Interictal spike connectivity is a novel approach to map epileptic networks that could help advance invasive and non-invasive epilepsy treatments.