Cryopreservation of ovarian cortex: therapeutic prospects and actuel considerations

info:eu-repo/semantics/published

Entorhinal cortex volume in older adults: reliability and validity considerations for three published measurement protocols.

Measuring the entorhinal cortex (ERC) is challenging due to lateral border discrimination from the perirhinal cortex. From a sample of 39 nondemented older adults who completed volumetric image scans and verbal memory indices, we examined reliability and validity concerns for three ERC protocols with different lateral boundary guidelines (i.e., Goncharova, Dickerson, Stoub, & deToledo-Morrell, 2001; Honeycutt et al., 1998; Insausti et al., 1998). We used three novice raters to assess inter-rater reliability on a subset of scans (216 total ERCs), with the entire dataset measured by one rater with strong intra-rater reliability on each technique (234 total ERCs). We found moderate to strong inter-rater reliability for two techniques with consistent ERC lateral boundary endpoints (Goncharova, Honeycutt), with negligible to moderate reliability for the technique requiring consideration of collateral sulcal depth (Insausti). Left ERC and story memory associations were moderate and positive for two techniques designed to exclude the perirhinal cortex (Insausti, Goncharova), with the Insausti technique continuing to explain 10% of memory score variance after additionally controlling for depression symptom severity. Right ERC-story memory associations were nonexistent after excluding an outlier. Researchers are encouraged to consider challenges of rater training for ERC techniques and how lateral boundary endpoints may impact structure-function associations.

Variability in frontotemporal brain structure: the importance of recruitment of African Americans in neuroscience research.

BACKGROUND: Variation in brain structure is both genetically and environmentally influenced. The question about potential differences in brain anatomy across populations of differing race and ethnicity remains a controversial issue. There are few studies specifically examining racial or ethnic differences and also few studies that test for race-related differences in context of other neuropsychiatric research, possibly due to the underrepresentation of ethnic minorities in clinical research. It is within this context that we conducted a secondary data analysis examining volumetric MRI data from healthy participants and compared the volumes of the amygdala, hippocampus, lateral ventricles, caudate nucleus, orbitofrontal cortex (OFC) and total cerebral volume between Caucasian and African-American participants. We discuss the importance of this finding in context of neuroimaging methodology, but also the need for improved recruitment of African Americans in clinical research and its broader implications for a better understanding of the neural basis of neuropsychiatric disorders. METHODOLOGY/PRINCIPAL FINDINGS: This was a case control study in the setting of an academic medical center outpatient service. Participants consisted of 44 Caucasians and 33 ethnic minorities. The following volumetric data were obtained: amygdala, hippocampus, lateral ventricles, caudate nucleus, orbitofrontal cortex (OFC) and total cerebrum. Each participant completed a 1.5 T magnetic resonance imaging (MRI). Our primary finding in analyses of brain subregions was that when compared to Caucasians, African Americans exhibited larger left OFC volumes (F (1,68) = 7.50, p = 0.008). CONCLUSIONS: The biological implications of our findings are unclear as we do not know what factors may be contributing to these observed differences. However, this study raises several questions that have important implications for the future of neuropsychiatric research.

Functional parcellation of attentional control regions of the brain.

Recently, a number of investigators have examined the neural loci of psychological processes enabling the control of visual spatial attention using cued-attention paradigms in combination with event-related functional magnetic resonance imaging. Findings from these studies have provided strong evidence for the involvement of a fronto-parietal network in attentional control. In the present study, we build upon this previous work to further investigate these attentional control systems. In particular, we employed additional controls for nonattentional sensory and interpretative aspects of cue processing to determine whether distinct regions in the fronto-parietal network are involved in different aspects of cue processing, such as cue-symbol interpretation and attentional orienting. In addition, we used shorter cue-target intervals that were closer to those used in the behavioral and event-related potential cueing literatures. Twenty participants performed a cued spatial attention task while brain activity was recorded with functional magnetic resonance imaging. We found functional specialization for different aspects of cue processing in the lateral and medial subregions of the frontal and parietal cortex. In particular, the medial subregions were more specific to the orienting of visual spatial attention, while the lateral subregions were associated with more general aspects of cue processing, such as cue-symbol interpretation. Additional cue-related effects included differential activations in midline frontal regions and pretarget enhancements in the thalamus and early visual cortical areas.

Resolving response, decision, and strategic control: evidence for a functional topography in dorsomedial prefrontal cortex.

The dorsomedial prefrontal cortex (DMPFC) plays a central role in aspects of cognitive control and decision making. Here, we provide evidence for an anterior-to-posterior topography within the DMPFC using tasks that evoke three distinct forms of control demands--response, decision, and strategic--each of which could be mapped onto independent behavioral data. Specifically, we identify three spatially distinct regions within the DMPFC: a posterior region associated with control demands evoked by multiple incompatible responses, a middle region associated with control demands evoked by the relative desirability of decision options, and an anterior region that predicts control demands related to deviations from an individual's preferred decision-making strategy. These results provide new insight into the functional organization of DMPFC and suggest how recent controversies about its role in complex decision making and response mapping can be reconciled.

When strangers pass: processing of mutual and averted social gaze in the superior temporal sulcus.

Using functional magnetic resonance imaging (fMRI), we investigated brain activity evoked by mutual and averted gaze in a compelling and commonly experienced social encounter. Through virtual-reality goggles, subjects viewed a man who walked toward them and shifted his neutral gaze either toward (mutual gaze) or away (averted gaze) from them. Robust activity was evoked in the superior temporal sulcus (STS) and fusiform gyrus (FFG). For both conditions, STS activity was strongly right lateralized. Mutual gaze evoked greater activity in the STS than did averted gaze, whereas the FFG responded equivalently to mutual and averted gaze. Thus, we show that the STS is involved in processing social information conveyed by shifts in gaze within an overtly social context. This study extends understanding of the role of the STS in social cognition and social perception by demonstrating that it is highly sensitive to the context in which a human action occurs.

Co-activation of the amygdala, hippocampus and inferior frontal gyrus during autobiographical memory retrieval.

Functional MRI was used to investigate the role of medial temporal lobe and inferior frontal lobe regions in autobiographical recall. Prior to scanning, participants generated cue words for 50 autobiographical memories and rated their phenomenological properties using our autobiographical memory questionnaire (AMQ). During scanning, the cue words were presented and participants pressed a button when they retrieved the associated memory. The autobiographical retrieval task was interleaved in an event-related design with a semantic retrieval task (category generation). Region-of-interest analyses showed greater activation of the amygdala, hippocampus, and right inferior frontal gyrus during autobiographical retrieval relative to semantic retrieval. In addition, the left inferior frontal gyrus showed a more prolonged duration of activation in the semantic retrieval condition. A targeted correlational analysis revealed pronounced functional connectivity among the amygdala, hippocampus, and right inferior frontal gyrus during autobiographical retrieval but not during semantic retrieval. These results support theories of autobiographical memory that hypothesize co-activation of frontotemporal areas during recollection of episodes from the personal past.

The neuropsychology of autobiographical memory.

This special issue of Cortex focuses on the relative contribution of different neural networks to memory and the interaction of 'core' memory processes with other cognitive processes. In this article, we examine both. Specifically, we identify cognitive processes other than encoding and retrieval that are thought to be involved in memory; we then examine the consequences of damage to brain regions that support these processes. This approach forces a consideration of the roles of brain regions outside of the frontal, medial-temporal, and diencephalic regions that form a central part of neurobiological theories of memory. Certain kinds of damage to visual cortex or lateral temporal cortex produced impairments of visual imagery or semantic memory; these patterns of impairment are associated with a unique pattern of amnesia that was distinctly different from the pattern associated with medial-temporal trauma. On the other hand, damage to language regions, auditory cortex, or parietal cortex produced impairments of language, auditory imagery, or spatial imagery; however, these impairments were not associated with amnesia. Therefore, a full model of autobiographical memory must consider cognitive processes that are not generally considered 'core processes,' as well as the brain regions upon which these processes depend.

Frontal-striatal circuits in cognitive aging: Evidence for caudate involvement

Changes in cognition with aging have been claimed to be due in large part to a decline in frontal lobe function. However, at our present state of knowledge, the emphasis on the frontal lobes to the exclusion of the rest of the frontal-striatal circuits of which they are a part is unwarranted. To argue this point, I consider another anatomical candidate within these circuits, the caudate. Evidence is presented that the caudate decreases in size with age as much as the frontal lobes and that damage to either the frontal lobes or the caudate is accompanied by declines in inhibitory processes, executive control, and cognitive speed similar to those seen in normal aging. Separating the unique contributions of the frontal lobes and the caudate to these circuits is difficult but should be the focus of future studies of the biological basis of cognitive aging.

Delay activity of saccade-related neurons in the caudal dentate nucleus of the macaque cerebellum.

The caudal dentate nucleus (DN) in lateral cerebellum is connected with two visual/oculomotor areas of the cerebrum: the frontal eye field and lateral intraparietal cortex. Many neurons in frontal eye field and lateral intraparietal cortex produce "delay activity" between stimulus and response that correlates with processes such as motor planning. Our hypothesis was that caudal DN neurons would have prominent delay activity as well. From lesion studies, we predicted that this activity would be related to self-timing, i.e., the triggering of saccades based on the internal monitoring of time. We recorded from neurons in the caudal DN of monkeys (Macaca mulatta) that made delayed saccades with or without a self-timing requirement. Most (84%) of the caudal DN neurons had delay activity. These neurons conveyed at least three types of information. First, their activity was often correlated, trial by trial, with saccade initiation. Correlations were found more frequently in a task that required self-timing of saccades (53% of neurons) than in a task that did not (27% of neurons). Second, the delay activity was often tuned for saccade direction (in 65% of neurons). This tuning emerged continuously during a trial. Third, the time course of delay activity associated with self-timed saccades differed significantly from that associated with visually guided saccades (in 71% of neurons). A minority of neurons had sensory-related activity. None had presaccadic bursts, in contrast to DN neurons recorded more rostrally. We conclude that caudal DN neurons convey saccade-related delay activity that may contribute to the motor preparation of when and where to move.

Less wiring, more firing: low-performing older adults compensate for impaired white matter with greater neural activity.

The reliable neuroimaging finding that older adults often show greater activity (over-recruitment) than younger adults is typically attributed to compensation. Yet, the neural mechanisms of over-recruitment in older adults (OAs) are largely unknown. Rodent electrophysiology studies have shown that as number of afferent fibers within a circuit decreases with age, the fibers that remain show higher synaptic field potentials (less wiring, more firing). Extrapolating to system-level measures in humans, we proposed and tested the hypothesis that greater activity in OAs compensates for impaired white-matter connectivity. Using a neuropsychological test battery, we measured individual differences in executive functions associated with the prefrontal cortex (PFC) and memory functions associated with the medial temporal lobes (MTLs). Using event-related functional magnetic resonance imaging, we compared activity for successful versus unsuccessful trials during a source memory task. Finally, we measured white-matter integrity using diffusion tensor imaging. The study yielded 3 main findings. First, low-executive OAs showed greater success-related activity in the PFC, whereas low-memory OAs showed greater success-related activity in the MTLs. Second, low-executive OAs displayed white-matter deficits in the PFC, whereas low-memory OAs displayed white-matter deficits in the MTLs. Finally, in both prefrontal and MTL regions, white-matter decline and success-related activations occurred in close proximity and were negatively correlated. This finding supports the less-wiring-more-firing hypothesis, which provides a testable account of compensatory over-recruitment in OAs.

Frontal eye field neurons assess visual stability across saccades.

The image on the retina may move because the eyes move, or because something in the visual scene moves. The brain is not fooled by this ambiguity. Even as we make saccades, we are able to detect whether visual objects remain stable or move. Here we test whether this ability to assess visual stability across saccades is present at the single-neuron level in the frontal eye field (FEF), an area that receives both visual input and information about imminent saccades. Our hypothesis was that neurons in the FEF report whether a visual stimulus remains stable or moves as a saccade is made. Monkeys made saccades in the presence of a visual stimulus outside of the receptive field. In some trials, the stimulus remained stable, but in other trials, it moved during the saccade. In every trial, the stimulus occupied the center of the receptive field after the saccade, thus evoking a reafferent visual response. We found that many FEF neurons signaled, in the strength and timing of their reafferent response, whether the stimulus had remained stable or moved. Reafferent responses were tuned for the amount of stimulus translation, and, in accordance with human psychophysics, tuning was better (more prevalent, stronger, and quicker) for stimuli that moved perpendicular, rather than parallel, to the saccade. Tuning was sometimes present as well for nonspatial transaccadic changes (in color, size, or both). Our results indicate that FEF neurons evaluate visual stability during saccades and may be general purpose detectors of transaccadic visual change.

Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder.

Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala-calcarine (P=0.01) and amygdala-thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala-ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.

Similar prevalence and magnitude of auditory-evoked and visually evoked activity in the frontal eye fields: implications for multisensory motor control.

Saccadic eye movements can be elicited by more than one type of sensory stimulus. This implies substantial transformations of signals originating in different sense organs as they reach a common motor output pathway. In this study, we compared the prevalence and magnitude of auditory- and visually evoked activity in a structure implicated in oculomotor processing, the primate frontal eye fields (FEF). We recorded from 324 single neurons while 2 monkeys performed delayed saccades to visual or auditory targets. We found that 64% of FEF neurons were active on presentation of auditory targets and 87% were active during auditory-guided saccades, compared with 75 and 84% for visual targets and saccades. As saccade onset approached, the average level of population activity in the FEF became indistinguishable on visual and auditory trials. FEF activity was better correlated with the movement vector than with the target location for both modalities. In summary, the large proportion of auditory-responsive neurons in the FEF, the similarity between visual and auditory activity levels at the time of the saccade, and the strong correlation between the activity and the saccade vector suggest that auditory signals undergo tailoring to match roughly the strength of visual signals present in the FEF, facilitating accessing of a common motor output pathway.