Preserved hippocampus activation in normal aging as revealed by fMRI

The hippocampus is deteriorated in various pathologies such as Alzheimer's disease (AD) and such deterioration has been linked to memory impairment. By contrast, the structural and functional effects of normal aging on the hippocampus is a matter of debate, with some findings suggesting deterioration and others providing evidence of preservation. This constitutes a crucial question since many investigations on AD are based on the assumption that the deterioration of the hippocampus is the breaking point between normal and pathological aging. A growing number of fMRI studies specifically aimed at investigating hippocampal engagement in various cognitive tasks, notably memory tasks, but the results have been inconclusive. Here, we optimized the episodic face‐name paired‐associates task in order to test the functioning of the hippocampus in normal aging. Critically, we found no difference in the activation of the hippocampus between the young and a group of older participants. Analysis of individual patterns of activation substantiated this impression. Collectively, these findings provide evidence of preserved hippocampal functioning in normal aging. © 2010 Wiley‐Liss, Inc.     

Age-related changes in object processing and contextual binding revealed using fMR adaptation

Using fMR adaptation, we studied the effects of aging on the neural processing of passively viewed naturalistic pictures composed of a prominent object against a background scene. Spatially distinct neural regions showing specific patterns of adaptation to objects, background scenes, and contextual integration (binding) were identified in young adults. Older adults did not show adaptation responses corresponding to binding in the medial-temporal areas. They also showed an adaptation deficit for objects whereby their lateral occipital complex (LOC) did not adapt to repeated objects in the context of a changing background. The LOC could be activated, however, when objects were presented without a background. Moreover, the adaptation deficit for objects viewed against backgrounds was reversed when elderly subjects were asked to attend to objects while viewing these complex pictures. These findings suggest that the elderly have difficulty with simultaneous processing of objects and backgrounds that, in turn, could contribute to deficient contextual binding.     

Prism adaptation in normal aging: slower adaptation rate and larger aftereffect

The effect of aging on prism adaptation, a motor learning paradigm, was evaluated. Different measures were obtained from a task consisting of throwing clay balls to a target in front of the subjects before, during, and after wearing prisms that deviate the visual field by several degrees. When performing the task without wearing the prisms, the aged subjects showed a larger hit variance, whereas the young subjects hit closer to the target. When donning the prisms, the aged group adapted more slowly than the controls, although after throwing all the balls both groups showed the same adaptation levels. After removing the prisms, the aged group showed a larger aftereffect. These findings suggest that the aftereffect requires the involvement of non-cognitive and cognitive processes and indicate that both adaptation and aftereffect are influenced by aging.     

fMRI during word processing in dyslexic and normal reading children

The present study addresses phonological processing in children with developmental dyslexia. Following the hypothesis of a core deficit of assembled phonology in dyslexia a set of hierarchically structured tasks was applied that specifically control for different kinds of phonological coding (assembled versus addressed phonological strategies). Seventeen developmental dyslexics and 17 normal reading children were scanned during four different tasks: (1) passive viewing of letter strings (control condition), (2) passive reading of non-words, (3) passive reading of legal words, and (4) a task requiring phonological transformation. Statistical analysis of the data was performed using statistical parametric mapping (SPM96). Comparison of patterns of activation in dyslexic and normal reading children revealed significant differences in Broca's area and the left inferior temporal region for both, non-word reading and the phonological transformation task. The present data provide new evidence for alteration of the phonological system in dyslexic children, and in particular, the system that mediates assembled phonological coding.     

Sarcolemmal excitability changes in normal human aging

Introduction: The exact mechanisms underlying the loss of skeletal muscle bulk and power with normal human aging are not well established. Recording of muscle velocity recovery cycles (MVRCs) is an in‐vivo neurophysiologic technique we employed to assess the impact of age on sarcolemmal excitability. Methods: MVRC recordings were obtained from tibialis anterior (n = 74) and rectus femoris (n = 32) muscles in 74 healthy subjects (18–84 years, median age 35 years, interquartile range 29–55 years). Results: Increasing age was linearly associated with longer muscle relative refractory period (MRRP) and reduced early supernormality (ESN) in both tibialis anterior (MRRP: r² = 0.38, P < 0.001; ESN: r² = 0.33, P < 0.001) and rectus femoris (MRRP: r² = 0.30, P = 0.002; ESN: r² = 0.19, P = 0.01) muscles. Discussion: The results are consistent with progressive depolarization of the resting sarcolemmal potential with normal aging. This may be an important mechanism in explaining age‐related muscle decline. Muscle Nerve 57 : 981–988, 2018     

Reorganization of sensory processing below the level of spinal cord injury as revealed by fMRI

The adult mammalian CNS undergoes plastic changes in response to injury. To investigate such changes in spinal cord, functional magnetic resonance imaging (fMRI) was applied in rats subjected to complete transection of the mid-thoracic spinal cord. Blood oxygenation level-dependent (BOLD) contrasts were recorded in the distal spinal cord different times after injury (3, 7, and 14 days, and 1, 3, and 6 months) in response to electrical hind limb stimulation. Functional MRI demonstrated a substantial increase of neuronal activation in the ipsilateral dorsal horn after injury. Notably, 0.5 mA, which did not evoke activation in the normal spinal cord and was considered a non-painful stimulus, induced significant BOLD responses in the dorsal horn after injury. Increased sensitivity was also seen in response to 1.0 mA stimulation. Our results suggest exaggerated responsiveness of spinal neurons after spinal cord injury. Reorganization in the injured spinal cord has been shown to involve the amplification of peripheral inputs and implicated as one underlying mechanism causing neuropathic pain and autonomic dysreflexia. Since BOLD signals can demonstrate such plastic changes in spinal cord parenchyma, we propose fMRI as a method to monitor functional reorganization in the spinal cord after injury. Combining brain and spinal cord fMRI allows the visualization of neuronal activities along the entire neuroaxis and thereby an evaluation of the different plastic responses to CNS injuries that occur in the brain and the spinal cord.     

Dynamic changes in the mental rotation network revealed by pattern recognition analysis of fMRI data

We investigated the temporal dynamics and changes in connectivity in the mental rotation network through the application of spatio-temporal support vector machines (SVMs). The spatio-temporal SVM [Mourao-Miranda, J., Friston, K. J., et al. (2007). Dynamic discrimination analysis: A spatial-temporal SVM. Neuroimage, 36, 88-99] is a pattern recognition approach that is suitable for investigating dynamic changes in the brain network during a complex mental task. It does not require a model describing each component of the task and the precise shape of the BOLD impulse response. By defining a time window including a cognitive event, one can use spatio-temporal fMRI observations from two cognitive states to train the SVM. During the training, the SVM finds the discriminating pattern between the two states and produces a discriminating weight vector encompassing both voxels and time (i.e., spatio-temporal maps). We showed that by applying spatio-temporal SVM to an event-related mental rotation experiment, it is possible to discriminate between different degrees of angular disparity (0 degrees vs. 20 degrees , 0 degrees vs. 60 degrees , and 0 degrees vs. 100 degrees ), and the discrimination accuracy is correlated with the difference in angular disparity between the conditions. For the comparison with highest accuracy (0 degrees vs. 100 degrees ), we evaluated how the most discriminating areas (visual regions, parietal regions, supplementary, and premotor areas) change their behavior over time. The frontal premotor regions became highly discriminating earlier than the superior parietal cortex. There seems to be a parcellation of the parietal regions with an earlier discrimination of the inferior parietal lobe in the mental rotation in relation to the superior parietal. The SVM also identified a network of regions that had a decrease in BOLD responses during the 100 degrees condition in relation to the 0 degrees condition (posterior cingulate, frontal, and superior temporal gyrus). This network was also highly discriminating between the two conditions. In addition, we investigated changes in functional connectivity between the most discriminating areas identified by the spatio-temporal SVM. We observed an increase in functional connectivity between almost all areas activated during the 100 degrees condition (bilateral inferior and superior parietal lobe, bilateral premotor area, and SMA) but not between the areas that showed a decrease in BOLD response during the 100 degrees condition.     

Real and imaginary rotary motion processing: functional parcellation of the human parietal lobe revealed by fMRI

Functional magnetic resonance imaging was performed in 16 healthy subjects while they undertook orientation discrimination tasks of real rotating and mentally rotating alphanumeric characters. Perception of rotating and stationary abstract characters was also performed. Mental rotation and the perception of alphanumeric characters undergoing real rotation activated equivalent cortical areas, in keeping with the analogue hypothesis of mental rotation. In addition, areas along the dorsal stream, including the V5/middle temporal complex and the intraparietal sulcus (IPS), were activated during both the real and imaginary rotary conditions. Within the parietal lobe there were areas of convergence (i.e., recruited by all three motion conditions) and areas of divergence (i.e., selectively activated by a particular condition). Tasks requiring canonical-mirror orientation discrimination revealed involvement of neural substrates localized to the ventrolateral bank of the IPS. Tasks in which this judgment was not performed and during which the subject viewed rotary motion of abstract stimuli recruited activity in the medial bank of the IPS. These results indicate subspecialization of the human posterior parietal lobe according to function.     

Individual differences in decision making competence revealed by multivariate fMRI

While an extensive literature in decision neuroscience has elucidated the neurobiological foundations of decision making, prior research has focused primarily on group‐level effects in a sample population. Due to the presence of inherent differences between individuals’ cognitive abilities, it is also important to examine the neural correlates of decision making that explain interindividual variability in cognitive performance. This study therefore investigated how individual differences in decision making competence, as measured by the Adult Decision Making Competence (A‐DMC) battery, are related to functional brain connectivity patterns derived from resting‐state fMRI data in a sample of 304 healthy participants. We examined connectome‐wide associations, identifying regions within frontal, parietal, temporal, and occipital cortex that demonstrated significant associations with decision making competence. We then assessed whether the functional interactions between brain regions sensitive to decision making competence and seven intrinsic connectivity networks (ICNs) were predictive of specific facets of decision making assessed by subtests of the A‐DMC battery. Our findings suggest that individual differences in specific facets of decision making competence are mediated by ICNs that support executive, social, and perceptual processes, and motivate an integrative framework for understanding the neural basis of individual differences in decision making competence.     

Pre-attentive detection of motion direction changes in normal aging

Effects of normal aging on pre-attentive detection of changes in motion direction were evaluated. Young, middle-aged, and older subjects performed a visual central task while standard and deviant gratings varying in motion direction were presented outside the focus of attention. A greater negativity in the event-related potentials (ERPs) to deviants was observed in all groups at posterior sites within the N2 latency range. Visual mismatch negativity (vMMN) reached its peak between 145 and 165 ms irrespective of age. However, significant age-related changes observed in vMMN mean amplitude may suggest that the pre-attentive visual detection become less efficient in older subjects. This could lead to age-related deficits in switching attention to potentially salient visual changes.     

Delays in neural processing during working memory encoding in normal aging

Declines in neural processing speed have been proposed to underlie a broad range of cognitive deficits in older adults. However, the impact of delays in neural processing during stimulus encoding on working memory (WM) performance is not well understood. In the current study, we assessed the influence of aging on the relationship between neural measures of processing speed and WM performance during a selective delayed-recognition task for color and motion stimuli, while electroencephalography (EEG) was recorded in young and older adults. A latency delay was observed for the selection negativity (SN) and alpha band activity (measures of attentional allocation) in older adults during WM encoding of both motion and color stimuli, with the latency and magnitude of the SN predicting subsequent recognition performance. Furthermore, an age-related delay in the N1 latency occurred specifically during the encoding of color stimuli. These results suggest that the presence of both generalized feature-based and feature-specific deficits in the speed of selective encoding of information contributes to WM performance deficits in older adults.     

Topographic EEG changes with normal aging and SDAT

EEG topography was compared in patients with senile dementia of the Alzheimer's type (SDAT), aged normal controls, and young normal controls to assess regional differences. The square root of absolute power was determined for each frequency using a Fast Fourier Transform (FFT). The normal elderly group showed a reduction in all 4 frequency bands, delta, theta, alpha and beta, at each of 32 leads when compared to the young controls. Z-transformation of the data revealed differences in topography. Older normals showed significantly greater mid-parietal and left mid-temporal delta than the younger controls. A similar pattern was seen for theta activity. Elderly controls showed relatively less occipital alpha and greater mid-parietal alpha. Beta activity demonstrated these same significant topographic differences. The elderly/SDAT comparison was significant for delta only. SDAT patients were characterized by a marked delta asymmetry in temporal regions which was not seen in the elderly normals.     

Repetition suppression for performed hand gestures revealed by fMRI

The functional components of the human motor system that are used to retrieve and execute simple intransitive hand gestures were identified with a repetition suppression (RS) paradigm. Participants performed movements with the right hand to text instructions in a rapid event related design with a pseudo‐random stimulus order. Brain areas associated with action retrieval were identified by comparing trials where an action was repeated to trials that involved a new action. Performance of a novel action, collapsed across individual actions, resulted in significantly greater activity in a left hemisphere predominant fronto‐parietal circuit involving inferior frontal gyrus and inferior parietal cortex (supramarginal gyrus). This is consistent with previous action retrieval tasks using go, no‐go paradigms and lesion studies of patients with apraxia that emphasize a role of these areas in action organization. In addition, RS effects were present in left primary sensorimotor cortex. These effects cannot be ascribed to kinematic differences, simple action related activity or differences of cognitive set. Significant RS effects for action retrieval could be identified with as little as 5 min of fMRI data and underscores the potential of using RS to characterize representational structure within the motor system. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

Prefrontal-subcortical dissociations underlying inhibitory control revealed by event-related fMRI

Using event-related fMRI, this study investigated the neural dynamics of response inhibition under fluctuating task demands. Fourteen participants performed a GO/NOGO task requiring inhibition of a prepotent motor response to NOGO events that occurred as part of either a Fast or Slow presentation stream of GO stimuli. We compared functional activations associated with correct withholds (Stops) required during the Fast presentation stream of stimuli to Stops required during the Slow presentation stream. A predominantly right hemispheric network was activated across conditions, consistent with previous studies. Furthermore, a functional dissociation of activations between conditions was observed. Slow Stops elicited additional activation in anterior dorsal and polar prefrontal cortex and left inferior parietal cortex. Fast Stops showed additional activation in a network that included right dorsolateral prefrontal cortex, insula and dorsal striatum. These results are discussed in terms of our understanding of the impact of preparation on the distributed network underlying response inhibition and the contribution of subcortical areas, such as the basal ganglia, to executive control processes.     

Auditory induced vestibular (otolithic) processing revealed by an independent component analysis: an fMRI parametric analysis

Journal of Neurology -     

Cerebral blood flow changes in normal aging: Spect measurements

Global and regional cerebral blood flow (CBF) were evaluated with single photon emission computerized tomography (SPECT) utilizing both ¹³³Xenon (¹³³Xe) (47 subjects, 47–82 years old) and ⁹⁹Tc-hexamethylpropyleneamine oxime (⁹⁹Tc-HMPAO) (27 subjects, 47–80 years old). The ¹³³Xe results showed: among total subjects, no age-related decline in global CBF, but a significant regional decline in the occipital lobe (p < 0.05); among men, significant age-related declines in global, frontal, temporal, occipital and right hemisphere CBF (all p < 0.05); among women, no age-related decline in global or regional CBF. The ⁹⁹Tc-HMPAO results showed no age-related decline in either global or regional perfusion among total subjects, men or women. These results suggest that age-related global and regional (including frontal lobe) CBF declines do not occur in healthy control subjects after the age of 45 years. However, gender differences in age-related CBF changes warrant further study.     

Impaired perceptual networks in temporal lobe epilepsy revealed by resting fMRI

Viewed as a neural network disorder, mesial temporal lobe epilepsy (mTLE) may cause widespread deficits in human brain functions. Impairments in cognitive functions such as memory and language have been well addressed, but perceptual deficits have only been considered in terms of behavioral data. Little imaging research on perceptual deficits in mTLE has been reported. The present study is expected to reveal impairments in the perceptual networks in patients with mTLE using fMRI. The fMRI-based independent component analysis (ICA) was applied to 33 patients with mTLE and 33 matched healthy controls. In light of the resting-state networks (RSNs) corresponding to the basal functions of visual, auditory, and sensorimotor systems, the ICA data of functional connectivity within these RSNs were compared between the patients and controls. Compared with the controls, the mTLE patients presented decreased functional connectivity within the regions of the auditory and sensorimotor networks, as well increased functional connectivity in the primary visual cortex and decreased functional connectivity in the bilateral MT+ areas of the visual network. Our neuroimaging results are in agreement with the previous findings that specific perceptual functions are impaired in mTLE. Furthermore, our findings in the visual network support the belief that the primary visual function is not impaired and that there may be deficits in the high-order visual function in mTLE. Our fMRI study may contribute to the understanding of neuropathophysiological mechanisms underlying perceptual impairments in mTLE.     

Reduced somatosensory hand representation in thalidomide-induced dysmelia as revealed by fMRI

The concept of cerebral plasticity suggests that the hand representation in somatosensory cortex is abnormal in congenital malformation disorders. To investigate this issue we studied 11 subjects with different degrees of upper extremity dysmelia due to thalidomide embryopathy in comparison to 10 control subjects. In the affected subjects fingers are typically missing in radio-ulnar order beginning with the thumb. Haemodynamic responses to electrical stimulation of the radial-most and ulnar-most fingers were measured in each subject using functional magnetic resonance tomography. The size of the hand area in the primary somatosensory cortex was estimated by calculating the Euclidian distance between corresponding activation peaks on the lateral postcentral gyrus. The cortical somatosensory hand representation was found to be significantly smaller in dysmelic subjects as compared with the control subjects (P <0.001). The shrinkage of the hand area was not proportional to the number of missing fingers. Furthermore, the cortical representation of the ulnar fingers in the dysmelic subjects was shifted towards the cortical thumb representation of the control group. We suggest that the unproportional reduction of the hand area together with the observed shift may reflect use-dependent rather than malformation-induced reorganization of the somatosensory hand area.