Hartmut Schütze

Experience-dependent plasticity of white-matter microstructure extends into old age

Experience-dependent alterations in the human brains white-matter microstructure occur in early adulthood, but it is unknown whether such plasticity extends throughout life. We used cognitive training, diffusion-tensor imaging (DTI), and structural MRI to investigate plasticity of the white-matter tracts that connect the left and right hemisphere of the frontal lobes. Over a period of about 180 days, 20 younger adults and 12 older adults trained for a total of one hundred and one 1-h sessions on a set of three working memory, three episodic memory, and six perceptual speed tasks. Control groups were assessed at pre- and post-test. Training affected several DTI metrics and increased the area of the anterior part of the corpus callosum. These alterations were of similar magnitude in younger and older adults. The findings indicate that experience-dependent plasticity of white-matter microstructure extends into old age and that disruptions of structural interhemispheric connectivity in old age, which are pronounced in aging, are modifiable by experience and amenable to treatment.

The role of hippocampus dysfunction in deficient memory encoding and positive symptoms in schizophrenia

BACKGROUND Declarative memory disturbances, known to substantially contribute to cognitive impairment in schizophrenia, have previously been attributed to prefrontal as well as hippocampal dysfunction. AIMS To characterize the role of prefrontal and mesolimbic/hippocampal dysfunction during memory encoding in schizophrenia. METHOD Neuronal activation in schizophrenia patients and controls was assessed using functional magnetic resonance imaging (fMRI) during encoding of words in a deep (semantic judgement) and shallow (case judgment) task. A free recall (no delay) and a recognition task (24h delay) were performed. RESULTS Free recall, but not recognition performance was reduced in patients. Reduced performance was correlated with positive symptoms which in turn were related to increased left hippocampal activity during successful encoding. Furthermore, schizophrenia patients displayed a hippocampal hyperactivity during deep encoding irrespective of encoding success along with a reduced anterior cingulate cortex (ACC) and dorsomedial prefrontal cortex (DMPFC) activity in successful encoding but an intact left inferior frontal cortex (LIFC) activity. CONCLUSIONS This study provides the first evidence directly linking positive symptoms and memory deficits to dysfunctional hippocampal hyperactivity. It thereby underscores the pivotal pathophysiological role of a hyperdopaminergic mesolimbic state in schizophrenia.

Functional phenotyping of successful aging in long-term memory: Preserved performance in the absence of neural compensation.

We investigated whether preservation of encoding‐related brain activity patterns in older age reflects successful aging in long‐term memory. Using a statistical matching technique, we identified groups of healthy older adults with different degrees of Functional Activity Deviation during Encoding (FADE) from young adults in a memory network comprising hippocampal, temporal, occipital, and retrosplenial regions. High FADE scores were associated with impairment in recollection, abnormal activity in the default mode network, and lower gray matter density in bilateral ventral prefrontal cortex and left rhinal cortex; a constellation previously associated with increased risk for dementia. Low FADE scores functionally phenotyped successful aging because recollection was well preserved and there was no evidence for compensatory prefrontal activation. Thus, for some individuals successful aging in long‐term memory reflects the preservation of a functionally specific memory network, and can occur in the absence of compensatory brain activity. ©2010 Wiley‐Liss, Inc.

Strong Evidence for Pattern Separation in Human Dentate Gyrus.

The hippocampus is proposed to be critical in distinguishing between similar experiences by performing pattern separation computations that create orthogonalized representations for related episodes. Previous neuroimaging studies have provided indirect evidence that the dentate gyrus (DG) and CA3 hippocampal subregions support pattern separation by inferring the nature of underlying representations from the observation of novelty signals. Here, we use ultra-high-resolution fMRI at 7 T and multivariate pattern analysis to provide compelling evidence that the DG subregion specifically sustains representations of similar scenes that are less overlapping than in other hippocampal (e.g., CA3) and medial temporal lobe regions (e.g., entorhinal cortex). Further, we provide evidence that novelty signals within the DG are stimulus specific rather than generic in nature. Our study, in providing a mechanistic link between novelty signals and the underlying representations, constitutes the first demonstration that the human DG performs pattern separation. SIGNIFICANCE STATEMENT A fundamental property of an episodic memory system is the ability to minimize interference between similar episodes. The dentate gyrus (DG) subregion of the hippocampus is widely viewed to realize this function through a computation referred to as pattern separation, which creates distinct nonoverlapping neural codes for individual events. Here, we leveraged 7 T fMRI to test the hypothesis that this region supports pattern separation. Our results demonstrate that the DG supports representations of similar scenes that are less overlapping than those in neighboring subregions. The current study therefore is the first to offer compelling evidence that the human DG supports pattern separation by obtaining critical empirical data at the representational level: the level where this computation is defined.

Ventilatory Protective Strategies during Thoracic Surgery Effects of Alveolar Recruitment Maneuver and Low-tidal Volume Ventilation on Lung Density Distribution

BACKGROUND The increased tidal volume (V(T)) applied to the ventilated lung during one-lung ventilation (OLV) enhances cyclic alveolar recruitment and mechanical stress. It is unknown whether alveolar recruitment maneuvers (ARMs) and reduced V(T) may influence tidal recruitment and lung density. Therefore, the effects of ARM and OLV with different V(T) on pulmonary gas/tissue distribution are examined. METHODS Eight anesthetized piglets were mechanically ventilated (V(T) = 10 ml/kg). A defined ARM was applied to the whole lung (40 cm H(2)O for 10 s). Spiral computed tomographic lung scans were acquired before and after ARM. Thereafter, the lungs were separated with an endobronchial blocker. The pigs were randomized to receive OLV in the dependent lung with a V(T) of either 5 or 10 ml/kg. Computed tomography was repeated during and after OLV. The voxels were categorized by density intervals (i.e., atelectasis, poorly aerated, normally aerated, or overaerated). Tidal recruitment was defined as the addition of gas to collapsed lung regions. RESULTS The dependent lung contained atelectatic (56 ± 10 ml), poorly aerated (183 ± 10 ml), and normally aerated (187 ± 29 ml) regions before ARM. After ARM, lung volume and aeration increased (426 ± 35 vs. 526 ± 69 ml). Respiratory compliance enhanced, and tidal recruitment decreased (95% vs. 79% of the whole end-expiratory lung volume). OLV with 10 ml/kg further increased aeration (atelectasis, 15 ± 2 ml; poorly aerated, 94 ± 24 ml; normally aerated, 580 ± 98 ml) and tidal recruitment (81% of the dependent lung). OLV with 5 ml/kg did not affect tidal recruitment or lung density distribution. (Data are given as mean ± SD.) CONCLUSIONS The ARM improves aeration and respiratory mechanics. In contrast to OLV with high V(T), OLV with reduced V(T) does not reinforce tidal recruitment, indicating decreased mechanical stress.

Laminar activity in the hippocampus and entorhinal cortex related to novelty and episodic encoding

The ability to form long-term memories for novel events depends on information processing within the hippocampus (HC) and entorhinal cortex (EC). The HC–EC circuitry shows a quantitative segregation of anatomical directionality into different neuronal layers. Whereas superficial EC layers mainly project to dentate gyrus (DG), CA3 and apical CA1 layers, HC output is primarily sent from pyramidal CA1 layers and subiculum to deep EC layers. Here we utilize this directionality information by measuring encoding activity within HC/EC subregions with 7 T high resolution functional magnetic resonance imaging (fMRI). Multivariate Bayes decoding within HC/EC subregions shows that processing of novel information most strongly engages the input structures (superficial EC and DG/CA2–3), whereas subsequent memory is more dependent on activation of output regions (deep EC and pyramidal CA1). This suggests that while novelty processing is strongly related to HC–EC input pathways, the memory fate of a novel stimulus depends more on HC–EC output.

Fiber density between rhinal cortex and activated ventrolateral prefrontal regions predicts episodic memory performance in humans

The prefrontal cortex (PFC) is assumed to contribute to goal-directed episodic encoding by exerting cognitive control on medial temporal lobe (MTL) memory processes. However, it is thus far unclear to what extent the contribution of PFC-MTL interactions to memory manifests at a structural anatomical level. We combined functional magnetic resonance imaging and fiber tracking based on diffusion tensor imaging in 28 young, healthy adults to quantify the density of white matter tracts between PFC regions that were activated during the encoding period of a verbal free-recall task and MTL subregions. Across the cohort, the strength of fiber bundles linking activated ventrolateral PFC regions and the rhinal cortex (comprising the peri- and entorhinal cortices) of the MTL correlated positively with free-recall performance. These direct white matter connections provide a basis through which activated regions in the PFC can interact with the MTL and contribute to interindividual differences in human episodic memory.

Basal forebrain integrity and cognitive memory profile in healthy aging

Age-related dysfunctions in cholinergic and dopaminergic neuromodulation are assumed to contribute to age-associated impairment of explicit memory. Both neurotransmitters also modulate attention, working memory, and processing speed. To date, in vivo evidence linking structural age-related changes in these neuromodulatory systems to dysfunction within or across these cognitive domains remains scarce. Using a factor analytical approach in a cross-sectional study including 86 healthy older (aged 55 to 83 years) and 24 young (aged 18 to 30 years) adults, we assessed the relationship between structural integrity-as measured by magnetization transfer ratio (MTR)-of the substantia nigra/ventral tegmental area (SN/VTA), main origin of dopaminergic projections, basal forebrain (major origin of cortical cholinergic projections), frontal white matter (FWM), and hippocampus to neuropsychological and psychosocial scores. Basal forebrain MTR and FWM changes correlated with a factor combining verbal learning and memory and working memory and, as indicated by measures of diffusion, were most likely due to vascular pathology. These findings suggest that frontal white matter integrity and cholinergic neuromodulation provide clues as to why age-related cognitive decline is often correlated across cognitive domains.

Lung computed tomography density distribution in a porcine model of one-lung ventilation

BACKGROUND One-lung ventilation (OLV) exposes the dependent lung to increased mechanical stress which may affect the postoperative course. This study evaluates regional pulmonary gas/tissue distribution in a porcine model of OLV. METHODS Nine anaesthetized and mechanically ventilated (V(T)=10 ml kg(-1), FI(O(2))=0.40, PEEP=5 cm H(2)O) pigs were studied. After lung separation by an endobronchial blocker, lateral thoracotomy and OLV were performed in six pigs. Three animals served as controls. Static end-expiratory and end-inspiratory spiral computed tomography (CT) scans were done before, during, and after OLV and at corresponding times in controls. CT images were analysed by defined regions of interest and summarized voxels were classified by defined lung X-ray density intervals (atelectasis, poorly aerated, normally aerated, and overaerated). RESULTS Dependent lungs contained poorly aerated regions and atelectasis with a significant tidal recruitment during conventional two-lung ventilation (TLV) before OLV (expiration vs inspiration: atelectasis 29% vs 14%; poorly aerated 66% vs 44%; normally aerated 4% vs 41% of the dependent lung volume, P<0.05). During OLV (V(T)=10 ml kg(-1)), cyclic recruitment was increased. The density spectrum of the ventilated lung changed from consolidation to aeration (expiration vs inspiration: atelectasis 10% vs 2%; poorly aerated 71% vs 18%; normally aerated 19% vs 79%, P<0.05). After OLV, increased aeration remained with less atelectasis and poorly aerated regions. Lung density distribution in the non-dependent lung of OLV pigs was unaltered after the period of complete lung collapse. CONCLUSIONS Cyclic tidal recruitment during OLV in pigs was associated with a persistent increase of aeration in the dependent lung.

A close relationship between verbal memory and SN/VTA integrity in young and older adults

Age-related dysfunction in dopaminergic neuromodulation is assumed to contribute to age-associated memory impairment. However, to date there are no in vivo data on how structural parameters of the substantia nigra/ventral tegmental area (SN/VTA), the main origin of dopaminergic projections, relate to memory performance in healthy young and older adults. We investigated this relationship in a cross-sectional study including data from the hippocampus and frontal white matter (FWM) and also assessing working memory span and attention. In groups of young and older adults matched for the variance of their age distribution, gender and body mass index, we observed a robust positive correlation between Magnetization Transfer Ratio (MTR)--a measure of structural integrity--of the SN/VTA and FWM with verbal learning and memory performance among older adults, while there was a negative correlation in the young. Two additional imaging parameters, anisotropy of diffusion and diffusion coefficient, suggested that in older adults FWM changes reflected vascular pathology while SN/VTA changes pointed towards neuronal loss and loss of water content. The negative correlation in the young possibly reflected maturational changes. Multiple regression analyses indicated that in both young and older adults, SN/VTA MTR explained more variance of verbal learning and memory than FWM MTR or hippocampal MTR, and contributed less to explaining variance of working memory span. Together these findings indicate that structural integrity in the SN/VTA has a relatively selective impact on verbal learning and memory and undergoes specific changes from young adulthood to older age that qualitatively differ from changes in the FWM and hippocampus.