Diverse Cortical Regions Research Articles

Developmental maturation of millimeter-scale functional networks across brain areas.

Interacting with the environment to process sensory information, generate perceptions, and shape behavior engages neural networks in brain areas with highly varied representations, ranging from unimodal sensory cortices to higher-order association areas. Recent work suggests a much greater degree of commonality across areas, with distributed and modular networks present in both sensory and non-sensory areas during early development. However, it is currently unknown whether this initially common modular structure undergoes an equally common developmental trajectory, or whether such a modular functional organization persists in some areas-such as primary visual cortex-but not others. Here we examine the development of network organization across diverse cortical regions in ferrets of both sexes using in vivo widefield calcium imaging of spontaneous activity. We find that all regions examined, including both primary sensory cortices (visual, auditory, and somatosensory-V1, A1, and S1, respectively) and higher order association areas (prefrontal and posterior parietal cortices) exhibit a largely similar pattern of changes over an approximately 3 week developmental period spanning eye opening and the transition to predominantly externally-driven sensory activity. We find that both a modular functional organization and millimeter-scale correlated networks remain present across all cortical areas examined. These networks weakened over development in most cortical areas, but strengthened in V1. Overall, the conserved maintenance of modular organization across different cortical areas suggests a common pathway of network refinement, and suggests that a modular organization-known to encode functional representations in visual areas-may be similarly engaged in highly diverse brain areas.

Damage to temporoparietal cortex is sufficient for impaired semantic control.

Semantic control allows us to focus semantic activation on currently relevant aspects of knowledge, even in the face of competition or when the required information is weakly encoded. Diverse cortical regions, including left prefrontal and posterior temporal cortex, are implicated in semantic control, however; the relative contribution of these regions is unclear. For the first time, we compared semantic aphasia (SA) patients with damage restricted to temporoparietal cortex (TPC; N=8) to patients with infarcts encompassing prefrontal cortex (PF+; N=22), to determine if prefrontal lesions are necessary for semantic control deficits. These SA groups were also compared with semantic dementia (SD; N=10), characterised by degraded semantic representations. We asked whether TPC cases with semantic impairment show controlled retrieval deficits equivalent to PF+cases or conceptual degradation similar to patients with SD. Independent of lesion location, the SA subgroups showed similarities, whereas SD patients showed a qualitatively distinct semantic impairment. Relative to SD, both TPC and PF+SA subgroups: (1) showed few correlations in performance across tasks with differing control demands, but a strong relationship between tasks of similar difficulty; (2) exhibited attenuated effects of lexical frequency and concept familiarity, (3) showed evidence of poor semantic regulation in their verbal output - performance on picture naming was substantially improved when provided with a phonological cue, and (4) showed effects of control demands, such as retrieval difficulty, which were equivalent in severity across TPC and PF+groups. These findings show that semantic impairment in SA is underpinned by damage to a distributed semantic control network, instantiated across anterior and posterior cortical areas.

Learning-related congruent and incongruent changes of excitation and inhibition in distinct cortical areas.

Excitatory and inhibitory neurons in diverse cortical regions are likely to contribute differentially to the transformation of sensory information into goal-directed motor plans. Here, we investigate the relative changes across mouse sensorimotor cortex in the activity of putative excitatory and inhibitory neurons-categorized as regular spiking (RS) or fast spiking (FS) according to their action potential (AP) waveform-comparing before and after learning of a whisker detection task with delayed licking as perceptual report. Surprisingly, we found that the whisker-evoked activity of RS versus FS neurons changed in opposite directions after learning in primary and secondary whisker motor cortices, while it changed similarly in primary and secondary orofacial motor cortices. Our results suggest that changes in the balance of excitation and inhibition in local circuits concurrent with changes in the long-range synaptic inputs in distinct cortical regions might contribute to performance of delayed sensory-to-motor transformation.

Mapping the Microstructure and Striae of the Human Olfactory Tract with Diffusion MRI.

The human sense of smell plays an important role in appetite and food intake, detecting environmental threats, social interactions, and memory processing. However, little is known about the neural circuity supporting its function. The olfactory tracts project from the olfactory bulb along the base of the frontal cortex, branching into several striae to meet diverse cortical regions. Historically, using diffusion magnetic resonance imaging (dMRI) to reconstruct the human olfactory tracts has been prevented by susceptibility and motion artifacts. Here, we used a dMRI method with readout segmentation of long variable echo-trains (RESOLVE) to minimize image distortions and characterize the human olfactory tracts in vivo. We collected high-resolution dMRI data from 25 healthy human participants (12 male and 13 female) and performed probabilistic tractography using constrained spherical deconvolution (CSD). At the individual subject level, we identified the lateral, medial, and intermediate striae with their respective cortical connections to the piriform cortex and amygdala (AMY), olfactory tubercle (OT), and anterior olfactory nucleus (AON). We combined individual results across subjects to create a normalized, probabilistic atlas of the olfactory tracts. We then investigated the relationship between olfactory perceptual scores and measures of white matter integrity, including mean diffusivity (MD). Importantly, we found that olfactory tract MD negatively correlated with odor discrimination performance. In summary, our results provide a detailed characterization of the connectivity of the human olfactory tracts and demonstrate an association between their structural integrity and olfactory perceptual function.SIGNIFICANCE STATEMENT This study provides the first detailed in vivo description of the cortical connectivity of the three olfactory tract striae in the human brain, using diffusion magnetic resonance imaging (dMRI). Additionally, we show that tract microstructure correlates with performance on an odor discrimination task, suggesting a link between the structural integrity of the olfactory tracts and odor perception. Lastly, we generated a normalized probabilistic atlas of the olfactory tracts that may be used in future research to study its integrity in health and disease.

Association of altered cortical gyrification and psychopathological symptoms in patients with first-episode drug-naïve schizophrenia.

Altered brain gyrification in diverse cortical regions has been reported in patients with schizophrenia, which possibly reflects deviations in early neurodevelopment. The main purpose of this study was to examine the relationship between clinical symptoms and abnormal cortical gyrification in drug-naïve patients with schizophrenia in a Chinese Han population. We calculated the whole-brain cortical gyrification of 41 patients with first-episode drug-naïve schizophrenia and 30 age- and sex-matched healthy controls. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the psychopathology of patients with schizophrenia. Our results showed that compared to healthy controls, patients had higher cortical gyrification in the left lateral occipital cortex, but lower cortical gyrification in the left transverse temporal cortex. Moreover, the cortical gyrification in the left entorhinal cortex and left fusiform were both positively correlated with the general psychopathology of PANSS. Our findings indicate that abnormal cortical gyrification has occurred in the early stage of schizophrenia, suggesting that abnormal cortical gyrification may play an important role in the pathogenesis and symptomatology of schizophrenia.

Increased brain gyrification in the schizophrenia spectrum.

Increased brain gyrification in diverse cortical regions has been reported in patients with schizophrenia, possibly reflecting deviations in early neurodevelopment. However, it remains unknown whether patients with schizotypal disorder exhibit similar changes. This magnetic resonance imaging study investigated brain gyrification in 46 patients with schizotypal disorder (29 male, 17 female), 101 patients with schizophrenia (55 male, 46 female), and 77 healthy controls (44 male, 33 female). T1-weighted magnetic resonance images were obtained for each participant. Using FreeSurfer software, the local gyrification index (LGI) of the entire cortex was compared across the groups. Both schizophrenia and schizotypal disorder patients showed a significantly higher LGI in diverse cortical regions, including the bilateral prefrontal and left parietal cortices, as compared with controls, but its extent was broader in schizophrenia especially for the right prefrontal and left occipital regions. No significant correlations were found between the LGI and clinical variables (e.g., symptom severity, medication) for either of the patient groups. Increased LGI in the frontoparietal regions was common to both patient groups and might represent vulnerability to schizophrenia, while more diverse changes in schizophrenia patients might be associated with the manifestation of florid psychosis.

Increased Occipital Gyrification and Development of Psychotic Disorders in Individuals With an At-Risk Mental State: A Multicenter Study

BackgroundAnomalies of brain gyrification have been reported in schizophrenia, possibly reflecting its neurodevelopmental pathology. However, it remains elusive whether individuals at risk for psychotic disorders exhibit deviated gyrification patterns, and whether such findings, if present, are predictive of transition to psychotic disorders. MethodsThis multicenter magnetic resonance imaging study investigated brain gyrification and its relationship to later transition to psychotic disorders in a large sample of at-risk mental state (ARMS) individuals. T1-weighted magnetic resonance imaging scans were obtained from 104 ARMS individuals, of whom 21 (20.2%) exhibited the transition to psychotic disorders during clinical follow-up (mean = 4.9 years, SD = 2.6 years), and 104 healthy control subjects at 4 different sites. The local gyrification index (LGI) of the entire cortex was compared across the groups using FreeSurfer software. ResultsCompared with the control subjects, ARMS individuals showed a significantly higher LGI in widespread cortical areas, including the bilateral frontal, temporal, parietal, and occipital regions, which was partly associated with prodromal symptomatology. ARMS individuals who exhibited the transition to psychotic disorders showed a significantly higher LGI in the left occipital region compared with individuals without transition. ConclusionsThese findings suggested that increased LGI in diverse cortical regions might represent vulnerability to psychopathology, while increased LGI in the left occipital cortex might be related to subsequent manifestation of florid psychotic disorders as a possible surrogate marker.

Knowing what from where: Hippocampal connectivity with temporoparietal cortex at rest is linked to individual differences in semantic and topographic memory

The hippocampus contributes to episodic, spatial and semantic aspects of memory, yet individual differences within and between these functions are not well-understood. In 136 healthy individuals, we investigated whether these differences reflect variation in the strength of connections between functionally-specialised segments of the hippocampus and diverse cortical regions that participate in different aspects of memory. Better topographical memory was associated with stronger connectivity between lingual gyrus and left anterior, rather than posterior, hippocampus. Better semantic memory was associated with increased connectivity between the intracalcarine/cuneus and left, rather than right, posterior hippocampus. Notably, we observed a double dissociation between semantic and topographical memory: better semantic memory was associated with stronger connectivity between left temporoparietal cortex and left anterior hippocampus, while better topographic memory was linked to stronger connectivity with right anterior hippocampus. Together these data support a division-of-labour account of hippocampal functioning: at the population level, differences in connectivity across the hippocampus reflect functional specialisation for different facets of memory, while variation in these connectivity patterns across individuals is associated with differences in the capacity to retrieve different types of information. In particular, within-hemisphere connectivity between hippocampus and left temporoparietal cortex supports conceptual processing at the expense of spatial ability.

Distributed Visual–Vestibular Processing in the Cerebral Cortex of Man and Macaque

Recent advances in understanding the neurobiological underpinnings of visual–vestibular interactions underlying self-motion perception are reviewed with an emphasis on comparisons between the macaque and human brains. In both species, several distinct cortical regions have been identified that are active during both visual and vestibular stimulation and in some of these there is clear evidence for sensory integration. Several possible cross-species homologies between cortical regions are identified. A key feature of cortical organization is that the same information is apparently represented in multiple, anatomically diverse cortical regions, suggesting that information about self-motion is used for different purposes in different brain regions.

Widespread Vestibular Activation of the Rodent Cortex

Much of our understanding of the neuronal mechanisms of spatial navigation is derived from chronic recordings in rodents in which head-direction, place, and grid cells have all been described. However, despite the proposed importance of self-reference information to these internal representations of space, their congruence with vestibular signaling remains unclear. Here we have undertaken brain-wide functional mapping using both fMRI and electrophysiological methods to directly determine the spatial extent, strength, and time course of vestibular signaling across the rat forebrain. We find distributed activity throughout thalamic, limbic, and particularly primary sensory cortical areas in addition to known head-direction pathways. We also observe activation of frontal regions, including infralimbic and cingulate cortices, indicating integration of vestibular information throughout functionally diverse cortical regions. These whole-brain activity maps therefore suggest a widespread contribution of vestibular signaling to a self-centered framework for multimodal sensorimotor integration in support of movement planning, execution, spatial navigation, and autonomic responses to gravito-inertial changes.

Sustaining high acetylcholine levels in the frontal cortex, but not retrosplenial cortex, recovers spatial memory performance in a rodent model of diencephalic amnesia.

Although the thalamus and/or mammillary bodies are the primary sites of neuropathology in cases of diencephalic amnesia such as Wernicke Korsakoff Syndrome (WKS), there is also functional deactivation of certain cortical regions that contribute to the cognitive dysfunction. Acetylcholine (ACh) is a key neurotransmitter that modulates neural processing within the cortex and between the thalamus and cortex. In the pyrithiamine-induced thiamine deficiency (PTD) rat model of WKS, there are significant reductions in cholinergic innervation and behaviorally stimulated ACh efflux in the frontal (FC) and retrosplenial (RSC) cortices. In the present study, ACh released levels were site-specifically amplified with physostigmine (0.5 μg, 1.0 μg) in the FC and the RSC, which was confirmed with in vivo microdialysis. Although physostigmine sustained high ACh levels in both cortical regions, the effects on spatial memory, assessed by spontaneous alternation, were different as a function of region (FC, RSC) and treatment (PTD, pair-fed [PF]). Higher ACh levels in the FC recovered the rate of alternation in PTD rats as well as reduced arm-reentry perseverative errors. However, higher ACh levels within the FC of PF rats exacerbated arm-reentry perseverative errors without significantly affecting alternation rates. Maintaining high ACh levels in the RSC had no procognitive effects in PTD rats, but rather impaired alternation behavior in PF rats. These results demonstrate that diverse cortical regions respond differently to intensified ACh levels-and the effects are dependent on thalamic pathology. Thus, pharmacotherapeutics aimed at enhancing cognitive functions must account for the unique features of cortical ACh stimulation and the connective circuitry with the thalamus.

Effect of auditory input on activations in infant diverse cortical regions during audiovisual processing

A fundamental question with regard to perceptual development is how multisensory information is processed in the brain during the early stages of development. Although a growing body of evidence has shown the early emergence of modality-specific functional differentiation of the cortical regions, the interplay between sensory inputs from different modalities in the developing brain is not well understood. To study the effects of auditory input during audio-visual processing in 3-month-old infants, we evaluated the spatiotemporal cortical hemodynamic responses of 50 infants while they perceived visual objects with or without accompanying sounds. The responses were measured using 94-channel near-infrared spectroscopy over the occipital, temporal, and frontal cortices. The effects of sound manipulation were pervasive throughout the diverse cortical regions and were specific to each cortical region. Visual stimuli co-occurring with sound induced the early-onset activation of the early auditory region, followed by activation of the other regions. Removal of the sound stimulus resulted in focal deactivation in the auditory regions and reduced activation in the early visual region, the association region of the temporal and parietal cortices, and the anterior prefrontal regions, suggesting multisensory interplay. In contrast, equivalent activations were observed in the lateral occipital and lateral prefrontal regions, regardless of sound manipulation. Our findings indicate that auditory input did not generally enhance overall activation in relation to visual perception, but rather induced specific changes in each cortical region. The present study implies that 3-month-old infants may perceive audio-visual multisensory inputs by using the global network of functionally differentiated cortical regions.

Domain or not domain? That is the question: Longitudinal semantic deterioration in Alzheimer’s disease

Category specific semantic impairment (e.g. living versus nonliving things) has been reported in association with various pathologies, including herpes simplex encephalitis and semantic dementia. However, evidence is inconsistent regarding whether this effect exists in diseases progressively impacting diverse cortical regions, such as Alzheimer’s disease (AD). Ceiling effects producing non-Gaussian distributions and poor control for confounds such as nuisance variables (e.g. familiarity) may contribute to this discrepancy. Fourteen AD patients were longitudinally studied examining category effects on three semantic tasks (picture naming, naming to description and word to picture matching) matched across domain on all known nuisance variables (NV). To address non-Gaussian distributions, we run bootstrap analyses to determine whether NV, semantic domain or control performance best predicted AD patient performance. Multiple hierarchical regression analyses revealed that, whilst NV accounted for most of the explained variance in patients in the three tasks, the influence of semantic domain was substantially lower. Individual logistic regression demonstrated a significant category effect in only a few patients and healthy controls. No significant qualitative changes were observed in patients over time. Our results confirm the importance of NVs as predictors of AD patient performance, suggesting that the role of semantic domain is not a useful predictor of the progressive deterioration in AD.

Context-dependent interpretation of words: Evidence for interactive neural processes

The meaning of a word usually depends on the context in which it occurs. This study investigated the neural mechanisms involved in computing word meanings that change as a function of syntactic context. Current semantic processing theories suggest that word meanings are retrieved from diverse cortical regions storing sensory–motor and other types of semantic information and are further integrated with context in left inferior frontal gyrus (LIFG). Our fMRI data indicate that brain activity in an area sensitive to motion and action semantics – the posterior middle temporal gyrus (PMTG) – is modulated by a word’s syntactic context. Ambiguous words such as bowl were presented in minimal disambiguating contexts indicating object (the bowl) or action (to bowl) meanings and were compared to low-ambiguity controls. Ambiguous words elicited more activity than low-ambiguity controls in LIFG and various meaning-related areas such as PMTG. Critically, ambiguous words also elicited more activity in to-contexts than the-contexts in PMTG and LIFG, suggesting that contextual integration strengthened the action meaning in both areas. The pattern of results suggests that the activation of lexical information in PMTG was sensitive to contextual disambiguating information and that processing context-dependent meanings may involve interactions between frontal and posterior areas.

Semantic impairment in stroke aphasia versus semantic dementia: a case-series comparison

Different neuropsychological populations implicate diverse cortical regions in semantic memory: semantic dementia (SD) is characterized by atrophy of the anterior temporal lobes whilst poor comprehension in stroke aphasia is associated with prefrontal or temporal-parietal infarcts. This study employed a case-series design to compare SD and comprehension-impaired stroke aphasic patients directly on the same battery of semantic tests. Although the two groups obtained broadly equivalent scores, they showed qualitatively different semantic deficits. The SD group showed strong correlations between different semantic tasks--regardless of input/output modality--and substantial consistency when a set of items was assessed several times. They were also highly sensitive to frequency/familiarity and made coordinate and superordinate semantic errors in picture naming. These findings support the notion that amodal semantic representations degrade in SD. The stroke aphasia group also showed multimodal deficits and consistency across different input modalities, but inconsistent performance on tasks requiring different types of semantic processing. They were insensitive to familiarity/frequency--instead, tests of semantic association were influenced by the ease with which relevant semantic relationships could be identified and distractors rejected. In addition, the aphasic patients made associative semantic errors in picture naming that SD patients did not make. The aphasic patients' picture naming performance improved considerably with phonemic cues suggesting that these patients retained knowledge that could not be accessed without contextual support. We propose that semantic cognition is supported by two interacting principal components: (i) a set of amodal representations (which progressively degrade in SD) and (ii) executive processes that help to direct and control semantic activation in a task-appropriate fashion (which are dysfunctional in comprehension-impaired stroke aphasic patients).

Learning and memory is reflected in the responses of reinforcement- related neurons in the primate basal forebrain

Certain basal forebrain neurons encode the learned reinforcement value of objects: they respond differentially to visual stimuli that signal availability of fruit juice (positively reinforcing) or saline (negatively reinforcing) obtained by lick responses in visual discrimination tasks. In this report we describe the rapid, learning-related changes in the responses of these neurons during the acquisition and reversal of the reinforcement contingency of a visual discrimination reversal task. The same neurons also responded differentially to novel and familiar stimuli in 2 recognition memory tasks, in which monkeys applied the learned rule that lick responses to novel stimuli elicited saline and responses to familiar stimuli elicited juice. These differential responses to novel and familiar stimuli thus reflected the reinforcement value of the stimuli. A single presentation of a novel or a familiar stimulus was sufficient to elicit a differential response which was maintained even when the stimulus had not been seen recently. The maintenance of the differential response indicates that these neurons are influenced by a durable memory for the stimuli, estimated to be 30 trials on average. These differential neurons were recorded in the substantia innominata, the diagonal band of Broca, and a periventricular region of the basal forebrain. The responses of the reinforcement-related neurons in these 3 regions were similar in most respects. These results support the conclusion that basal forebrain neurons respond to sensory stimuli that, through learning of different contingencies, signal the availability of reinforcement. We suggest that the properties of learning and memory reflected in these neuronal responses are due to afferent pathways from ventromedial regions of the prefrontal and temporal cortices and the amygdala, and that the responses of these neurons provide an enabling mechanism that facilitates the operation of diverse cortical regions in which specific sensory, motor, or mnemonic functions take place.