Longitudinal changes in regional cerebral blood flow in late middle-aged and older adults with treated and untreated obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with abnormal cerebral perfusion at wakefulness, but whether these anomalies evolve over time is unknown. Here, we examined longitudinal changes in regional cerebral blood flow (rCBF) distribution in late middle-aged and older adults with treated or untreated OSA. Twelve controls (64.8 ± 8.0 years) and 23 participants with newly diagnosed OSA (67.8 ± 6.2 years) were evaluated with polysomnography and cerebral 99m Tc-HMPAO single-photon emission computed tomography during wakeful rest. OSA participants were referred to a sleep apnea clinic and 13 of them decided to start continuous positive airway pressure (CPAP). Participants were tested again after 18 months. Voxel-based analysis and extracted relative rCBF values were used to assess longitudinal changes. Untreated OSA participants showed decreased relative rCBF in the left hippocampus and the right parahippocampal gyrus over time, while treated participants showed trends for increased relative rCBF in the left hippocampus and the right parahippocampal gyrus. No changes were found over time in controls. Untreated OSA is associated with worsening relative rCBF in specific brain areas over time, while treated OSA shows the opposite. Considering that OSA possibly accelerates cognitive decline in older adults, CPAP treatment could help reduce risk for cognitive impairment.

Altered thalamic connectivity in insomnia disorder during wakefulness and sleep.

Insomnia disorder is the most common sleep disorder and has drawn increasing attention. Many studies have shown that hyperarousal plays a key role in the pathophysiology of insomnia disorder. However, the specific brain mechanisms underlying insomnia disorder remain unclear. To elucidate the neuropathophysiology of insomnia disorder, we investigated the brain functional networks of patients with insomnia disorder and healthy controls across the sleep-wake cycle. EEG-fMRI data from 33 patients with insomnia disorder and 31 well-matched healthy controls during wakefulness and nonrapid eye movement sleep, including N1, N2 and N3 stages, were analyzed. A medial and anterior thalamic region was selected as the seed considering its role in sleep-wake regulation. The functional connectivity between the thalamic seed and voxels across the brain was calculated. ANOVA with factors "group" and "stage" was performed on thalamus-based functional connectivity. Correlations between the misperception index and altered functional connectivity were explored. A group-by-stage interaction was observed at widespread cortical regions. Regarding the main effect of group, patients with insomnia disorder demonstrated decreased thalamic connectivity with the left amygdala, parahippocampal gyrus, putamen, pallidum and hippocampus across wakefulness and all three nonrapid eye movement sleep stages. The thalamic connectivity in the subcortical cluster and the right temporal cluster in N1 was significantly correlated with the misperception index. This study demonstrated the brain functional basis in insomnia disorder and illustrated its relationship with sleep misperception, shedding new light on the brain mechanisms of insomnia disorder and indicating potential therapeutic targets for its treatment.

Top-down and Bottom-up Regulated Auditory Phantom Perception.

Auditory phantom percepts such as tinnitus are associated with auditory deafferentation. The idea is that auditory deafferentation limits the amount of information the brain can acquire to make sense of the world. Because of this, auditory deafferentation increases the uncertainty of the auditory environment. To minimize uncertainty, the deafferented brain will attempt to obtain or fill in the missing information. A proposed multiphase compensation model suggests two distinct types of bottom-up related tinnitus: an auditory cortex related tinnitus and a parahippocampal cortex related tinnitus. The weakness of this model is that it cannot explain why some people without hearing loss develop tinnitus, whereas conversely others with hearing loss do not develop tinnitus. In this human study, we provide evidence for a top-down type of tinnitus associated with a deficient noise-cancelling mechanism. A total of 72 participants (age: 40.96 ± 7.67 years; males: 48; females: 24) were recruited for this study. We demonstrate that top-down related tinnitus is related to a change in the pregenual anterior cingulate cortex that corresponds to increased activity in the auditory cortex. This is in accordance with the idea that tinnitus can have different generators as proposed in a recent model that suggests that different compensation mechanisms at a cortical level can be linked to phantom percepts.SIGNIFICANCE STATEMENT Chronic tinnitus affects 15% of the population worldwide. The term "tinnitus" however represents a highly heterogeneous condition, as evidenced by the fact that there are no effective treatments or even an adequate understanding of the underlying neural mechanisms. Consistent with this idea, our research shows that tinnitus indeed has different subtypes related to hearing loss. In a human study tightly controlled for hearing loss, we establish a tinnitus subtype associated with a deficient top-down noise-cancelling mechanism, which distinguishes it from bottom-up subtypes. We demonstrate that top-down related tinnitus relates to a change in the pregenual anterior cingulate cortex that corresponds to increased activity in the auditory cortex, whereas bottom-up tinnitus instead relates to changes in the parahippocampal cortex.

The correlation between the electroencephalographic spectral analysis and salivary cortisol rhythm in insomnia.

OBJECTIVE: Insomnia is a common sleep disorder that affects many adults either transiently or chronically. This study aimed to establish whether there is a relationship between the electroencephalographic (EEG) spectral analysis and salivary cortisol levels in insomnia and compared to healthy controls. MATERIALS AND METHODS: This case-control study included 15 insomnia patients and 15 healthy control subjects. Insomnia was determined according to the International Classification of Headache Disorders III diagnostic criteria. The EEG data were collected and processed with MATLAB software. Blood and salivary samples were taken for hematological and biochemical measurements. Salivary cortisol levels were calculated and compared statistically with the healthy group. RESULTS: The mean age of the patients was 46.5 ± 11 years. The salivary cortisol levels at 18:00 and 24:00 were found higher in the insomnia than in the healthy subjects (respectively, 0.12 (0.11) µg/dl, 0.07 (0.02) µg/dl). But this difference was not statistically significant (p > 0.05). No significant difference was observed in the spectral analysis of patients between the frontal, central, and occipital channel (p > 0.05). However, in the correlation between the frontal channel spectral analysis and at the 24:00 salivary cortisol of patient and control group, DeltaGmax (p = 0.002), DeltaGmean (p = 0.019) and, in the correlation with 18:00 salivary cortisol DeltaGmax (p = 0.010), were positively correlated. CONCLUSION: In this study, no significant difference was found in spectral analysis and salivary cortisol levels in insomnia patients, but at 18:00 and 24:00, cortisol levels were correlated positively with theta and delta waves in EEG spectral analysis in some channels.

Effect-size seed-based d mapping of resting-state fMRI for persistent insomnia disorder.

BACKGROUND: Recently, several functional neuroimaging studies have been conducted in patients with persistent insomnia disorder, but these studies have yielded diverse findings. We aimed to identify convergence in function across the heterogeneity of patients, modalities, and methods for insomnia disorder by performing a quantitative coordinate-based meta-analysis. MATERIALS AND METHODS: We performed a quantitative, voxel-wise meta-analysis of resting-state fMRI studies using seed-based d mapping to find convergence of functional alterations in persistent insomnia disorder. RESULTS: We included 28 studies comprising 287 peak foci involving 951 patients with insomnia disorder and 884 healthy controls. Patients with persistent insomnia disorder showed that increased activity was more frequently reported in right parahippocampal gyrus (p < 0.001) and left median cingulate/paracingulate gyri (p < 0.001); while decreased activity was more frequently reported in right cerebellum (p < 0.001) and left superior frontal gyrus/medial orbital (p < 0.001). CONCLUSION: The altered functional networks in patients with persistent insomnia disorder converge in median cingulate/paracingulate gyri and right parahippocampal gyrus with increased activity, and cerebellum and superior frontal gyrus/medial orbital with reduced activity. As a potential target in future, the identification of these altered or unbalanced networks is very important because they may be noninvasively rebalanced to sleep homeostasis by noninvasive brain stimulation methods.

Human Parahippocampal Cortex Supports Spatial Binding in Visual Working Memory.

Studies investigating the functional organization of the medial temporal lobe (MTL) suggest that parahippocampal cortex (PHC) generates representations of spatial and contextual information used by the hippocampus in the formation of episodic memories. However, evidence from animal studies also implicates PHC in spatial binding of visual information held in short term, working memory. Here we examined a 46-year-old man (P.J.), after he had recovered from bilateral medial occipitotemporal cortex strokes resulting in ischemic lesions of PHC and hippocampal atrophy, and a group of age-matched healthy controls. When recalling the color of 1 of 2 objects, P.J. misidentified the target when cued by its location, but not shape. When recalling the position of 1 of 3 objects, he frequently misidentified the target, which was cued by its color. Increasing the duration of the memory delay had no impact on the proportion of binding errors, but did significantly worsen recall precision in both P.J. and controls. We conclude that PHC may play a crucial role in spatial binding during encoding of visual information in working memory.

Domain Selectivity in the Parahippocampal Gyrus Is Predicted by the Same Structural Connectivity Patterns in Blind and Sighted Individuals.

Human ventral occipital temporal cortex contains clusters of neurons that show domain-preferring responses during visual perception. Recent studies have reported that some of these clusters show surprisingly similar domain selectivity in congenitally blind participants performing nonvisual tasks. An important open question is whether these functional similarities are driven by similar innate connections in blind and sighted groups. Here we addressed this question focusing on the parahippocampal gyrus (PHG), a region that is selective for large objects and scenes. Based on the assumption that patterns of long-range connectivity shape local computation, we examined whether domain selectivity in PHG is driven by similar structural connectivity patterns in the two populations. Multiple regression models were built to predict the selectivity of PHG voxels for large human-made objects from white matter (WM) connectivity patterns in both groups. These models were then tested using independent data from participants with similar visual experience (two sighted groups) and using data from participants with different visual experience (blind and sighted groups). Strikingly, the WM-based predictions between blind and sighted groups were as successful as predictions between two independent sighted groups. That is, the functional selectivity for large objects of a PHG voxel in a blind participant could be accurately predicted by its WM pattern using the connection-to-function model built from the sighted group data, and vice versa. Regions that significantly predicted PHG selectivity were located in temporal and frontal cortices in both sighted and blind populations. These results show that the large-scale network driving domain selectivity in PHG is independent of vision.SIGNIFICANCE STATEMENT Recent studies have reported intriguingly similar domain selectivity in sighted and congenitally blind individuals in regions within the ventral visual cortex. To examine whether these similarities originate from similar innate connectional roots, we investigated whether the domain selectivity in one population could be predicted by the structural connectivity pattern of the other. We found that the selectivity for large objects of a PHG voxel in a blind participant could be predicted by its structural connectivity pattern using the connection-to-function model built from the sighted group data, and vice versa. These results reveal that the structural connectivity underlying domain selectivity in the PHG is independent of visual experience, providing evidence for nonvisual representations in this region.

Distress-dependent temporal variability of regions encoding domain-specific and domain-general behavioral manifestations of phantom percepts.

Tinnitus is the perception of a phantom sound characterized behaviorally by a loudness and a distress component. Although a wealth of information is available about the relationship between these behavioral correlates and changes in static functional connectivity, its relationship with dynamic changes in network connectivity is yet unexplored. The aim of this study was thus to investigate changes in the flexibility and stability of temporal variability in tinnitus and its relation to loudness and distress using continuous resting-state EEG. We observe an increase in temporal variability at the whole-brain level in tinnitus, which is spatiotemporally distributed at the nodal level. Behaviorally, we observe changes in the relationship between temporal variability and loudness and distress depending on the amount of distress experienced. In patients with low distress, there is no relationship between temporal variability and loudness or distress, demonstrating a resilience in dynamic connectivity of the brain. However, patients with high distress exhibit a direct relationship with increasing loudness in the primary auditory cortex and parahippocampus, and an inverse relationship with increasing distress in the parahippocampus. In tinnitus, the specific sensory (loudness) component related to increased temporal variability possibly reflects a Bayesian search for updating deafferentation-based missing information. On the other hand, the decreased temporal variability related to the nonspecific distress component possibly reflects a more hard-wired or less adaptive contextual processing. Therefore, our findings may reveal a way to understand the changes in network dynamics not just in tinnitus, but also in other brain disorders.

Respiration pattern variability and related default mode network connectivity are altered in remitted depression.

BACKGROUND: Studies with healthy participants and patients with respiratory diseases suggest a relation between respiration and mood. The aim of the present analyses was to investigate whether emotionally challenged remitted depressed participants show higher respiration pattern variability (RPV) and whether this is related to mood, clinical outcome and increased default mode network connectivity. METHODS: To challenge participants, sad mood was induced with keywords of personal negative life events in individuals with remitted depression [recurrent major depressive disorder (rMDD), n = 30] and matched healthy controls (HCs, n = 30) during functional magnetic resonance imaging. Respiration was measured by means of a built-in respiration belt. Additionally, questionnaires, a daily life assessment of mood and a 3 years follow-up were applied. For replication, we analysed RPV in an independent sample of 53 rMDD who underwent the same fMRI paradigm. RESULTS: During sad mood, rMDD compared with HC showed greater RPV, with higher variability in pause duration and respiration frequency and lower expiration to inspiration ratio. Higher RPV was related to lower daily life mood and predicted higher depression scores as well as relapses during a 3-year follow-up period. Furthermore, in rMDD compared with HC higher main respiration frequency exhibited a more positive association with connectivity of the posterior cingulate cortex and the right parahippocampal gyrus. CONCLUSIONS: The results suggest a relation between RPV, mood and depression on the behavioural and neural level. Based on our findings, we propose interventions focusing on respiration to be a promising additional tool in the treatment of depression.

Facial emotion processing in patients with seizure disorders.

Studies of emotion processing are needed to better understand the pathophysiology of psychogenic nonepileptic seizures (PNES). We examined the differences in facial emotion processing between 12 patients with PNES, 12 patients with temporal lobe epilepsy (TLE), and 24 matched healthy controls (HCs) using fMRI with emotional faces task (EFT) (happy/sad/fearful/neutral) and resting state connectivity. Compared with TLE, patients with PNES exhibited increased fMRI response to happy, neutral, and fearful faces in visual, temporal, and/or parietal regions and decreased fMRI response to sad faces in the putamen bilaterally. Regions showing significant differences between PNES and TLE were used as functional seed regions of interest (ROIs), in addition to amygdala structural seed ROIs for resting state functional connectivity analyses. Whole brain analyses showed that compared with TLE and HCs, patients with PNES exhibited increased functional connectivity of the functional seed ROIs to several brain regions, particularly to cerebellar, visual, motor, and frontotemporal regions. Connectograms showed increased functional connections between left parahippocampal gyrus/uncus ROIs and right temporal ROIs in PNES compared with both the TLE and HC groups. Resting state functional connectivity of the left and right amygdala to various brain regions including emotion regulation and motor control circuits was increased in PNES when compared with those with TLE. This study provides preliminary evidence that patients with PNES exhibit altered facial emotion processing compared with patients with TLE and HCs and increased amygdala functional connectivity compared with TLE. These findings identify potential key differences in facial emotion processing reflective of neurophysiologic markers of neural circuitry alterations that can be used to generate further hypotheses for developing studies that examine the contributions of emotion processing to the development and maintenance of PNES.

Parahippocampal and Entorhinal Resection Extent Predicts Verbal Memory Decline in an Epilepsy Surgery Cohort.

The differential contribution of medial-temporal lobe regions to verbal declarative memory is debated within the neuroscience, neuropsychology, and cognitive psychology communities. We evaluate whether the extent of surgical resection within medial-temporal regions predicts longitudinal verbal learning and memory outcomes. This single-center retrospective observational study involved patients with refractory temporal lobe epilepsy undergoing unilateral anterior temporal lobe resection from 2007 to 2015. Thirty-two participants with Engel Class 1 and 2 outcomes were included (14 left, 18 right) and followed for a mean of 2.3 years after surgery (±1.5 years). Participants had baseline and postsurgical neuropsychological testing and high-resolution T1-weighted MRI scans. Postsurgical lesions were manually traced and coregistered to presurgical scans to precisely quantify resection extent of medial-temporal regions. Verbal learning and memory change scores were regressed on hippocampal, entorhinal, and parahippocampal resection volume after accounting for baseline performance. Overall, there were no significant differences in learning and memory change between patients who received left and right anterior temporal lobe resection. After controlling for baseline performance, the extent of left parahippocampal resection accounted for 27% (p = .021) of the variance in verbal short delay free recall. The extent of left entorhinal resection accounted for 37% (p = .004) of the variance in verbal short delay free recall. Our findings highlight the critical role that the left parahippocampal and entorhinal regions play in recall for verbal material.

Autobiographical memory: a candidate latent vulnerability mechanism for psychiatric disorder following childhood maltreatment.

BackgroundAltered autobiographical memory (ABM) functioning has been implicated in the pathogenesis of depression and post-traumatic stress disorder and may represent one mechanism by which childhood maltreatment elevates psychiatric risk.AimsTo investigate the impact of childhood maltreatment on ABM functioning.MethodThirty-four children with documented maltreatment and 33 matched controls recalled specific ABMs in response to emotionally valenced cue words during functional magnetic resonance imaging.ResultsChildren with maltreatment experience showed reduced hippocampal and increased middle temporal and parahippocampal activation during positive ABM recall compared with peers. During negative ABM recall they exhibited increased amygdala activation, and greater amygdala connectivity with the salience network.ConclusionsChildhood maltreatment is associated with altered ABM functioning, specifically reduced activation in areas encoding specification of positive memories, and greater activation of the salience network for negative memories. This pattern may confer latent vulnerability to future depression and post-traumatic stress disorder.

Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia.

SEE BIGLER DOI101093/AWW277 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterized by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the default mode network. Interactions within the default mode network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the default mode network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. Nineteen patients with traumatic brain injury were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory, patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normalized when these functions improved. We have previously shown abnormally high posterior cingulate cortex connectivity in the chronic phase after traumatic brain injury, and this abnormality was also observed in patients with post-traumatic amnesia. Patients with post-traumatic amnesia showed evidence of widespread traumatic axonal injury measured using diffusion magnetic resonance imaging. This change was more marked within the cingulum bundle, the tract connecting the parahippocampal gyrus to the posterior cingulate cortex. These findings provide novel insights into the pathophysiology of post-traumatic amnesia and evidence that memory impairment acutely after traumatic brain injury results from altered parahippocampal functional connectivity, perhaps secondary to the effects of axonal injury on white matter tracts connecting limbic structures involved in memory processing.

Reduced functional connectivity between bilateral precuneus and contralateral parahippocampus in schizotypal personality disorder.

BACKGROUND: Schizotypal personality disorder (SPD) is linked to schizophrenia in terms of shared genetics, biological markers and phenomenological characteristics. In the current study, we aimed to determine whether the previously reported altered functional connectivity (FC) with precuneus in patients with schizophrenia could be extended to individuals with SPD. METHODS: Twenty subjects with SPD and 19 healthy controls were recruited from 4461 freshmen at a university in Shanghai and received a resting-state scan of MRI. All participants were evaluated by the Chinese version of Schizotypal Personality Questionnaire (SPQ) and the Chinese version of Symptom Checklist (SCL-90). The imaging data were analysed using the seed-based functional connectivity method. RESULTS: Compared with the controls, SPD subjects exhibited reduced FC between bilateral precuneus and contralateral parahippocampus. In SPD group, SPQ total score was negatively correlated with FC between right precuneus and left parahippocampus (r = -0.603, p = 0.006); there was a negative trend between SPQ subscale score of suspiciousness and FC between left precuneus and right parahippocampus (r = -0.553, p = 0.014); and a positive trend was found between SPQ subscale score of odd or eccentric behaviour and FC between left precuneus and right superior temporal gyrus (r = 0.543, p = 0.016). As for the SCL-90 score, a similar negative trend was found between SCL-90 subscale score of suspiciousness and FC between right precuneus and left parahippocampus (r = -0.535, p = 0.018) in SPD group. CONCLUSIONS: Our findings suggest that the decreased functional connectivity between precuneus and contralateral parahippocampus might play a key role in the pathophysiology of schizophrenia spectrum disorder.

Deafferentation-based pathophysiological differences in phantom sound: Tinnitus with and without hearing loss.

Tinnitus has been considered an auditory phantom percept. Recently a theoretical multiphase compensation mechanism at a cortical level has been hypothesized linking auditory deafferentation to tinnitus. This Bayesian brain model predicts that two very different kinds of tinnitus should exist, depending on the amount of hearing loss: an auditory cortex related form of tinnitus not associated with hearing loss, and a (para)hippocampal form associated with hearing loss, in which the auditory cortex might be of little relevance. In order to verify this model, resting state source analyzed EEG recordings were made in 129 tinnitus patients, and correlated to the mean hearing loss, the range of the hearing loss and the hearing loss at the tinnitus frequency. Results demonstrate that tinnitus can be linked to 2 very different mechanisms. In patients with little or no hearing loss, the tinnitus seems to be more related to auditory cortex activity, but not to (para)hippocampal memory related activity, whereas in tinnitus patients with more severe hearing loss, tinnitus seems to be related to (para)hippocampal mechanisms. Furthermore hearing loss seems to drive the communication between the auditory cortex and the parahippocampus, as measured by functional and effective connectivity.

Emotion Reactivity and Cerebrovascular Burden in Late-Life GAD: A Neuroimaging Study.

OBJECTIVE: Generalized anxiety disorder (GAD) in older adults is associated with persistent deficits in emotion reactivity (ER) and regulation, yet the neural basis of these deficits has not been explored. This study focuses on the neural basis of ER deficits in late-life GAD and the association with cerebrovascular burden. METHODS: Twenty elderly nonanxious participants and 17 late-life GAD participants were included. The faces-shapes functional magnetic resonance imaging task was used to assess ER; the Hamilton Anxiety Rating Scale and the Penn State Worry Questionnaire to measure global anxiety and worry, respectively; linear regression models to examine the association between ER and global anxiety severity and between ER and worry severity; and mediation analysis to explore the effect of ER on the relationship between global anxiety/worry severity and cerebrovascular burden. RESULTS: A positive association was found between ER and global anxiety in the left parahippocampus, left and right precuneus, and right superior occipital gyrus. A negative association was found between ER and worry severity in the left and right precuneus. The association between cerebrovascular burden and anxiety/worry severity was indirectly mediated by increased ER in limbic and paralimbic areas and by decreased ER in prefrontal regulatory regions. CONCLUSION: These results indicate that ER is associated with different neural activation patterns for worry and global anxiety and that ER-related functional connectivity indirectly mediates the relationship between cerebrovascular burden and late-life GAD. This latter result supports a yet-unexplored cerebrovascular pathway involved in the pathophysiology of late-life anxiety.

Seeing scenes: topographic visual hallucinations evoked by direct electrical stimulation of the parahippocampal place area.

In recent years, functional neuroimaging has disclosed a network of cortical areas in the basal temporal lobe that selectively respond to visual scenes, including the parahippocampal place area (PPA). Beyond the observation that lesions involving the PPA cause topographic disorientation, there is little causal evidence linking neural activity in that area to the perception of places. Here, we combined functional magnetic resonance imaging (fMRI) and intracranial EEG (iEEG) recordings to delineate place-selective cortex in a patient implanted with stereo-EEG electrodes for presurgical evaluation of drug-resistant epilepsy. Bipolar direct electrical stimulation of a cortical area in the collateral sulcus and medial fusiform gyrus, which was place-selective according to both fMRI and iEEG, induced a topographic visual hallucination: the patient described seeing indoor and outdoor scenes that included views of the neighborhood he lives in. By contrast, stimulating the more lateral aspect of the basal temporal lobe caused distortion of the patient's perception of faces, as recently reported (Parvizi et al., 2012). Our results support the causal role of the PPA in the perception of visual scenes, demonstrate that electrical stimulation of higher order visual areas can induce complex hallucinations, and also reaffirm direct electrical brain stimulation as a tool to assess the function of the human cerebral cortex.

Layer-specific modulation of entorhinal cortical excitability by presubiculum in a rat model of temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and is often refractory to antiepileptic medications. The medial entorhinal area (MEA) is affected in TLE but mechanisms underlying hyperexcitability of MEA neurons require further elucidation. Previous studies suggest that inputs from the presubiculum (PrS) contribute to MEA pathophysiology. We assessed electrophysiologically how PrS influences MEA excitability using the rat pilocarpine model of TLE. PrS-MEA connectivity was confirmed by electrically stimulating PrS afferents while recording from neurons within superficial layers of MEA. Assessment of alterations in PrS-mediated synaptic drive to MEA neurons was made following focal application of either glutamate or NBQX to the PrS in control and epileptic animals. Here, we report that monosynaptic inputs to MEA from PrS neurons are conserved in epileptic rats, and that PrS modulation of MEA excitability is layer-specific. PrS contributes more to synaptic inhibition of LII stellate cells than excitation. Under epileptic conditions, stellate cell inhibition is significantly reduced while excitatory synaptic drive is maintained at levels similar to control. PrS contributes to both synaptic excitation and inhibition of LIII pyramidal cells in control animals. Under epileptic conditions, overall excitatory synaptic drive to these neurons is enhanced while inhibitory synaptic drive is maintained at control levels. Additionally, neither glutamate nor NBQX applied focally to PrS now affected EPSC and IPSC frequency of LIII pyramidal neurons. These layer-specific changes in PrS-MEA interactions are unexpected and of significance in unraveling pathophysiological mechanisms underlying TLE.

Multimodal neuroimaging evidence of alterations in cortical structure and function in HIV-infected older adults.

Combination antiretroviral therapy transformed human immunodeficiency virus (HIV)-infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in frontoparietal networks of HIV-infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high-resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV-related cognitive impairments. HIV-infected adults and individually matched controls completed 3-Tesla structural magnetic resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data were examined using advanced beamforming methods, and sMRI data were analyzed using the latest voxel-based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV-infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially coincident with abnormal MEG responses in HIV-infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV-associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV-associated cognitive impairment, and may hold promise as a potential disease marker.

Individual differences in rumination in healthy and depressive samples: association with brain structure, functional connectivity and depression.

BACKGROUND: Rumination is an important cognitive risk factor for onset and relapse of depression. However, no studies have employed a dimensional approach in investigating the neural correlates of rumination and the relationship with depression. METHOD: Non-clinical healthy subjects (n = 306), who completed the classical rumination and depression scales, were studied using voxel-based morphometry and regional homogeneity (ReHo). Subsequently, mediation analysis was conducted to examine the influence of rumination on the relationship between brain structure and depression. Moreover, depressive patients (n = 60) and a control group (n = 63) of comparable age and education were studied with regions of interest that were identified in the healthy individuals. RESULTS: For healthy individuals, regional grey-matter volume (rGMV) of dorsolateral prefrontal cortex (DLPFC) and parahippocampal gyrus (PHG) were positively correlated with rumination. In addition, rumination had a mediating effect on the relationship between the DLPFC and PHG and depression. Moreover, ReHo analysis showed that rumination had a significantly negative correlation with functional homogeneity of DLPFC. However, compared to the control group, depressed patients showed significant decrease of rGMV in the DLPFC and PHG and there was a significant negative correlation between DLPFC volume and depressive rumination. CONCLUSIONS: Increased DLPFC volume (decreased ReHo) in healthy individuals while decreased in depression indicated the trend of DLPFC from inefficient inhibition ('overload state') to impaired regulatory mechanism ('paralysis state'). This finding might elucidate when and why healthy individuals would develop sustained negative mood and depression eventually.