The effects of hippocampal lesions on MRI measures of structural and functional connectivity.

Focal lesions can affect connectivity between distal brain regions (connectional diaschisis) and impact the graph-theoretic properties of major brain networks (connectomic diaschisis). Given its unique anatomy and diverse range of functions, the hippocampus has been claimed to be a critical "hub" in brain networks. We investigated the effects of hippocampal lesions on structural and functional connectivity in six patients with amnesia, using a range of magnetic resonance imaging (MRI) analyses. Neuropsychological assessment revealed marked episodic memory impairment and generally intact performance across other cognitive domains. The hippocampus was the only brain structure exhibiting reduced grey-matter volume that was consistent across patients, and the fornix was the only major white-matter tract to show altered structural connectivity according to both diffusion metrics. Nonetheless, functional MRI revealed both increases and decreases in functional connectivity. Analysis at the level of regions within the default-mode network revealed reduced functional connectivity, including between nonhippocampal regions (connectional diaschisis). Analysis at the level of functional networks revealed reduced connectivity between thalamic and precuneus networks, but increased connectivity between the default-mode network and frontal executive network. The overall functional connectome showed evidence of increased functional segregation in patients (connectomic diaschisis). Together, these results point to dynamic reorganization following hippocampal lesions, with both decreased and increased functional connectivity involving limbic-diencephalic structures and larger-scale networks. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.Medical Research Council (Grant ID: MC-A060-5PR10); Biotechnology and Biological Sciences Research Council (Grant ID: BB/L02263X/1); Netherlands Organization for Scientific ResearchThis is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/hipo.2262

No effect of hippocampal lesions on stimulus-response bindings.

The hippocampus is believed to be important for rapid learning of arbitrary stimulus-response contingencies, or S-R bindings. In support of this, Schnyer et al. (2006) (Experiment 2) measured priming of reaction times (RTs) to categorise visual objects, and found that patients with medial temporal lobe damage, unlike healthy controls, failed to show evidence of reduced priming when response contingencies were reversed between initial and repeated categorisation of objects (a signature of S-R bindings). We ran a similar though extended object classification task on 6 patients who appear to have selective hippocampal lesions, together with 24 age-matched controls. Unlike Schnyer et al. (2006), we found that reversing response contingencies abolished priming in both controls and patients. Bayes Factors provided no reason to believe that response reversal had less effect on patients than controls. We therefore conclude that it is unlikely that the hippocampus is needed for S-R bindings

Differentiation of semantic dementia and Alzheimer's disease using the Addenbrooke's Cognitive Examination (ACE)

BACKGROUND: The Addenbrooke's Cognitive Examination (ACE) is a simple diagnostic tool bridging the gap between the very brief Mini Mental State Exam (MMSE) and much longer test batteries used by neuropsychologists which has proven extremely popular internationally. OBJECTIVE: We aimed to assess the ability of the ACE to differentiate semantic dementia (SD) from Alzheimer's disease (AD). METHODS: The ACE was administered to three groups: SD patients (n = 40) and two separate groups of AD patients (n = 40 in each), matched for overall ACE or MMSE score. RESULTS: Significant differences were found between SD and both AD groups for the ACE sub-scores of naming, reading and orientation in time. Discriminant analysis (SD versus AD) led to the formulation of a 'semantic index' (naming plus reading minus scores for serial-7s, orientation in time and drawing). Application of the semantic index to the patient data found values of less than zero to be predictive of SD rather than AD with 88% sensitivity and 90% specificity. Validation analysis in an independent sample of 24 SD and AD patients proved even more favourable. CONCLUSIONS: The overall ACE score is known to be a sensitive, and specific, indicator of early neurodegenerative dementia; this study shows that the ACE can also be used to detect SD through application of the semantic index

Causal Contributions of the Domain-General (Multiple Demand) and the Language-Selective Brain Networks to Perceptual and Semantic Challenges in Speech Comprehension.

Funder: McGovern Institute for Brain ResearchListening to spoken language engages domain-general multiple demand (MD; frontoparietal) regions of the human brain, in addition to domain-selective (frontotemporal) language regions, particularly when comprehension is challenging. However, there is limited evidence that the MD network makes a functional contribution to core aspects of understanding language. In a behavioural study of volunteers (n = 19) with chronic brain lesions, but without aphasia, we assessed the causal role of these networks in perceiving, comprehending, and adapting to spoken sentences made more challenging by acoustic-degradation or lexico-semantic ambiguity. We measured perception of and adaptation to acoustically degraded (noise-vocoded) sentences with a word report task before and after training. Participants with greater damage to MD but not language regions required more vocoder channels to achieve 50% word report, indicating impaired perception. Perception improved following training, reflecting adaptation to acoustic degradation, but adaptation was unrelated to lesion location or extent. Comprehension of spoken sentences with semantically ambiguous words was measured with a sentence coherence judgement task. Accuracy was high and unaffected by lesion location or extent. Adaptation to semantic ambiguity was measured in a subsequent word association task, which showed that availability of lower-frequency meanings of ambiguous words increased following their comprehension (word-meaning priming). Word-meaning priming was reduced for participants with greater damage to language but not MD regions. Language and MD networks make dissociable contributions to challenging speech comprehension: Using recent experience to update word meaning preferences depends on language-selective regions, whereas the domain-general MD network plays a causal role in reporting words from degraded speech