An exploration of worry content and catastrophic thinking in middle-aged and older-aged adults with and without Parkinson's disease

Objective: Worry is a common and distressing problem in Parkinson’s disease(PD). However, little is known about the nature and content of worry in PD and how it might differ to non-PD populations. The study aimed to explore the content and nature of worry in middle and older aged adults with and without PD. Method: 4 groups of participants: 20 PD patients(10 high worry, 10 low worry) 19 middle and older aged adults(10 high worry, 9 low worry) completed the Catastrophising Interview(CI) for three worry topics. Worriers were classified(high/low) based on Penn State Worry Questionnaire scores. Data were analysed using Framework Analysis. Results: High worriers showed a greater diversity of worry topics than low worriers. Health worries differentiated high and low worriers in the non-PD sample but were common across all PD participants. The CI revealed that the root concern of worry was often different to that initially described. In particular, PD high worriers were more likely to express underlying concerns about negative self-perception and death/severe incapacity. Conclusion: The CI was able to identify the root cause of worry, demonstrating the value of this technique in the exploration and treatment of worry and psychological distress. Exploring worry content may help to distinguish patients with problematic worry, with worries about self-perception and death/severe incapacity characteristic of high worriers. Therapeutic interventions designed to alleviate problematic worry and distress in PD need to take account of the realities of living with PD and the potentially realistic nature of worries which may appear catastrophic in a healthy population

Bimodal coupling of ripples and slower oscillations during sleep in patients with focal epilepsy.

OBJECTIVE: Differentiating pathologic and physiologic high-frequency oscillations (HFOs) is challenging. In patients with focal epilepsy, HFOs occur during the transitional periods between the up and down state of slow waves. The preferred phase angles of this form of phase-event amplitude coupling are bimodally distributed, and the ripples (80-150 Hz) that occur during the up-down transition more often occur in the seizure-onset zone (SOZ). We investigated if bimodal ripple coupling was also evident for faster sleep oscillations, and could identify the SOZ. METHODS: Using an automated ripple detector, we identified ripple events in 40-60 min intracranial electroencephalography (iEEG) recordings from 23 patients with medically refractory mesial temporal lobe or neocortical epilepsy. The detector quantified epochs of sleep oscillations and computed instantaneous phase. We utilized a ripple phasor transform, ripple-triggered averaging, and circular statistics to investigate phase event-amplitude coupling. RESULTS: We found that at some individual recording sites, ripple event amplitude was coupled with the sleep oscillatory phase and the preferred phase angles exhibited two distinct clusters (p \u3c 0.05). The distribution of the pooled mean preferred phase angle, defined by combining the means from each cluster at each individual recording site, also exhibited two distinct clusters (p \u3c 0.05). Based on the range of preferred phase angles defined by these two clusters, we partitioned each ripple event at each recording site into two groups: depth iEEG peak-trough and trough-peak. The mean ripple rates of the two groups in the SOZ and non-SOZ (NSOZ) were compared. We found that in the frontal (spindle, p = 0.009; theta, p = 0.006, slow, p = 0.004) and parietal lobe (theta, p = 0.007, delta, p = 0.002, slow, p = 0.001) the SOZ incidence rate for the ripples occurring during the trough-peak transition was significantly increased. SIGNIFICANCE: Phase-event amplitude coupling between ripples and sleep oscillations may be useful to distinguish pathologic and physiologic events in patients with frontal and parietal SOZ

Electrophysiological Signatures of Spatial Boundaries in the Human Subiculum.

Environmental boundaries play a crucial role in spatial navigation and memory across a wide range of distantly related species. In rodents, boundary representations have been identified at the single-cell level in the subiculum and entorhinal cortex of the hippocampal formation. Although studies of hippocampal function and spatial behavior suggest that similar representations might exist in humans, boundary-related neural activity has not been identified electrophysiologically in humans until now. To address this gap in the literature, we analyzed intracranial recordings from the hippocampal formation of surgical epilepsy patients (of both sexes) while they performed a virtual spatial navigation task and compared the power in three frequency bands (1-4, 4-10, and 30-90 Hz) for target locations near and far from the environmental boundaries. Our results suggest that encoding locations near boundaries elicited stronger theta oscillations than for target locations near the center of the environment and that this difference cannot be explained by variables such as trial length, speed, movement, or performance. These findings provide direct evidence of boundary-dependent neural activity localized in humans to the subiculum, the homolog of the hippocampal subregion in which most boundary cells are found in rodents, and indicate that this system can represent attended locations that rather than the position of one\u27s own body

Human Verbal Memory Encoding Is Hierarchically Distributed in a Continuous Processing Stream.

Processing of memory is supported by coordinated activity in a network of sensory, association, and motor brain regions. It remains a major challenge to determine where memory is encoded for later retrieval. Here, we used direct intracranial brain recordings from epilepsy patients performing free recall tasks to determine the temporal pattern and anatomical distribution of verbal memory encoding across the entire human cortex. High γ frequency activity (65-115 Hz) showed consistent power responses during encoding of subsequently recalled and forgotten words on a subset of electrodes localized in 16 distinct cortical areas activated in the tasks. More of the high γ power during word encoding, and less power before and after the word presentation, was characteristic of successful recall and observed across multiple brain regions. Latencies of the induced power changes and this subsequent memory effect (SME) between the recalled and forgotten words followed an anatomical sequence from visual to prefrontal cortical areas. Finally, the magnitude of the memory effect was unexpectedly found to be the largest in selected brain regions both at the top and at the bottom of the processing stream. These included the language processing areas of the prefrontal cortex and the early visual areas at the junction of the occipital and temporal lobes. Our results provide evidence for distributed encoding of verbal memory organized along a hierarchical posterior-to-anterior processing stream

Electrical Stimulation Modulates High γ Activity and Human Memory Performance.

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62-118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with poor memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation

White Matter Network Architecture Guides Direct Electrical Stimulation Through Optimal State Transitions

Electrical brain stimulation is currently being investigated as a therapy for neurological disease. However, opportunities to optimize such therapies are challenged by the fact that the beneficial impact of focal stimulation on both neighboring and distant regions is not well understood. Here, we use network control theory to build a model of brain network function that makes predictions about how stimulation spreads through the brain's white matter network and influences large-scale dynamics. We test these predictions using combined electrocorticography (ECoG) and diffusion weighted imaging (DWI) data who volunteered to participate in an extensive stimulation regimen. We posit a specific model-based manner in which white matter tracts constrain stimulation, defining its capacity to drive the brain to new states, including states associated with successful memory encoding. In a first validation of our model, we find that the true pattern of white matter tracts can be used to more accurately predict the state transitions induced by direct electrical stimulation than the artificial patterns of null models. We then use a targeted optimal control framework to solve for the optimal energy required to drive the brain to a given state. We show that, intuitively, our model predicts larger energy requirements when starting from states that are farther away from a target memory state. We then suggest testable hypotheses about which structural properties will lead to efficient stimulation for improving memory based on energy requirements. Our work demonstrates that individual white matter architecture plays a vital role in guiding the dynamics of direct electrical stimulation, more generally offering empirical support for the utility of network control theoretic models of brain response to stimulation

Ripples Have Distinct Spectral Properties and Phase-Amplitude Coupling With Slow Waves, but Indistinct Unit Firing, in Human Epileptogenic Hippocampus

Ripple oscillations (80–200 Hz) in the normal hippocampus are involved in memory consolidation during rest and sleep. In the epileptic brain, increased ripple and fast ripple (200–600 Hz) rates serve as a biomarker of epileptogenic brain. We report that both ripples and fast ripples exhibit a preferred phase angle of coupling with the trough-peak (or On-Off) state transition of the sleep slow wave in the hippocampal seizure onset zone (SOZ). Ripples on slow waves in the hippocampal SOZ also had a lower power, greater spectral frequency, and shorter duration than those in the non-SOZ. Slow waves in the mesial temporal lobe modulated the baseline firing rate of excitatory neurons, but did not significantly influence the increased firing rate associated with ripples. In summary, pathological ripples and fast ripples occur preferentially during the On-Off state transition of the slow wave in the epileptogenic hippocampus, and ripples do not require the increased recruitment of excitatory neurons.Fil: Weiss, Shennan A.. Thomas Jefferson University; Estados UnidosFil: Song, Inkyung. Thomas Jefferson University; Estados UnidosFil: Leng, Mei. University of California at Los Angeles; Estados UnidosFil: Pastore, Tomás. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; ArgentinaFil: Fernandez Slezak, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Investigación en Ciencias de la Computación. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Investigación en Ciencias de la Computación; ArgentinaFil: Waldman, Zachary. Thomas Jefferson University; Estados UnidosFil: Orosz, Iren. University of California at Los Angeles; Estados UnidosFil: Gorniak, Richard. Thomas Jefferson University; Estados UnidosFil: Donmez, Mustafa. Thomas Jefferson University; Estados UnidosFil: Sharan, Ashwini. Thomas Jefferson University; Estados UnidosFil: Wu, Chengyuan. Thomas Jefferson University; Estados UnidosFil: Fried, Itzhak. University of California at Los Angeles; Estados UnidosFil: Sperling, Michael R.. Thomas Jefferson University; Estados UnidosFil: Bragin, Anatol. University of California at Los Angeles; Estados UnidosFil: Engel, Jerome. University of California at Los Angeles; Estados UnidosFil: Nir, Yuval. Tel Aviv University; IsraelFil: Staba, Richard. University of California at Los Angeles; Estados Unido

Contribution of the drought tolerance-related stress-responsive NAC1 transcription factor to resistance of barley to Ramularia leaf spot

NAC proteins are plant transcription factors that are involved in tolerance to abiotic and biotic stresses, as well as in many developmental processes. Stress-responsive NAC1 (SNAC1) transcription factor is involved in drought tolerance in barley and rice, but has not been shown previously to have a role in disease resistance. Transgenic over-expression of HvSNAC1 in barley cv. Golden Promise reduced the severity of Ramularia leaf spot (RLS), caused by the fungus Ramularia collo-cygni, but had no effect on disease symptoms caused by Fusarium culmorum, Oculimacula yallundae (eyespot), Blumeria graminis f. sp. hordei (powdery mildew) or Magnaporthe oryzae (blast). The HvSNAC1 transcript was weakly induced in the RLS-susceptible cv. Golden Promise during the latter stages of R. collo-cygni symptom development when infected leaves were senescing. Potential mechanisms controlling HvSNAC1-mediated resistance to RLS were investigated. Gene expression analysis revealed no difference in the constitutive levels of antioxidant transcripts in either of the over-expression lines compared with cv. Golden Promise, nor was any difference in stomatal conductance or sensitivity to reactive oxygen species-induced cell death observed. Over-expression of HvSNAC1 delayed dark-induced leaf senescence. It is proposed that mechanisms controlled by HvSNAC1 that are involved in tolerance to abiotic stress and that inhibit senescence also confer resistance to R. collo-cygni and suppress RLS symptoms. This provides further evidence for an association between abiotic stress and senescence in barley and the development of RLS

Lateralized hippocampal oscillations underlie distinct aspects of human spatial memory and navigation

The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1–3-Hz “low theta” band increases when viewing subsequently remembered object–location pairs. In contrast, in the right but not left hippocampus, low-theta activity increases during periods of navigation. The frequencies of these hippocampal signals are slower than task-related signals in the neocortex. These results suggest that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition

Mechanical adaptation of trabecular bone morphology in the mammalian mandible

Alveolar bone, together with the underlying trabecular bone, fulfils an important role in providing structural support against masticatory forces. Diseases such as osteoporosis or periodontitis cause alveolar bone resorption which weakens this structural support and is a major cause of tooth loss. However, the functional relationship between alveolar bone remodelling within the molar region and masticatory forces is not well understood. This study investigated this relationship by comparing mammalian species with different diets and functional loading (Felis catus, Cercocebus atys, Homo sapiens, Sus scrofa, Oryctolagus cuniculus, Ovis aries). We performed histomorphometric analyses of trabecular bone morphology (bone volume fraction, trabecular thickness and trabecular spacing) and quantified the variation of bone and tooth root volumes along the tooth row. A principal component analysis and non-parametric MANOVA showed statistically significant differences in trabecular bone morphology between species with contrasting functional loading, but these differences were not seen in sub-adult specimens. Our results support a strong, but complex link between masticatory function and trabecular bone morphology. Further understanding of a potential functional relationship could aid the diagnosis and treatment of mandibular diseases causing alveolar bone resorption, and guide the design and evaluation of dental implants