The hippocampal region is necessary for text comprehension and memorization: a combined VBM/DTI study in neuropsychological patients.

According to the Construction-Integration model (Kintsch 1988; Kintsch 1998), two forms of representation are activated during the reading and the comprehension of a text: 1) the text base, which includes semantic propositions and 2) the situation model, corresponding to the integration of the information contained in the text to the memories and knowledge of the reader. Functional neuroimaging studies in healthy subjects have shown that the text base is underpinned by frontal regions and lateral temporal regions whereas the situation model would rather depend on the posterior cingulate cortex, the precuneus and other regions depending on the dimension studied. However, the brain regions highlighted so far were only involved in comprehension and not necessary for this cognitive ability. For the first time, we explored the brain structures necessary to understand texts using a combined VBM/DTI approach in neuropsychological patients with whom we obtained comprehension scores (text base and situation model) after the reading of narrative texts. To our great surprise and contrary to our hypotheses, which were based on the results of functional neuroimaging studies, our own results show that it is the hippocampal region that is necessary to activate and memorize/remember the text base and the situation model. The highlighting of a link between the integrity of a portion of the uncinate fasciculus which is well known to play a role in semantic processing and the performance scores of the text base suggests that the hippocampal region is necessary not only for the retrieval of the text base and of the situation model thanks to episodic memory, but also for the activation of the text base during the reading and the comprehension of a text.

Functional parcellation of the lateral mesencephalus.

The mesencephalic locomotor region (MLR), which includes the pedunculopontine nucleus (PPN) and the cuneiform nucleus (CN), has been recently identified as a key structure for locomotion and gait control in mammals. However, the function and the precise anatomy of the MLR remain unclear in humans. To study the lateral mesencephalus, we used fMRI in 15 right-handed healthy volunteers performing two tasks: imagine walking in a hallway and imagine an object moving along the same hallway. Both tasks were performed at two different speeds: normal and 30% faster. We identified two distinct networks of cortical activation: one involving motor/premotor cortices and the cerebellum for the walking task and the other involving posterior parietal and dorsolateral prefrontal cortices for the object moving task. In the lateral mesencephalus, we found that two different but anatomically connected parts of the MLR were activated during the fast condition of each task. The CN and the dorsal part of the PPN were activated during the fast imaginary walking task, whereas the ventral part of the PPN and the ventral part of the reticular formation were activated while subjects were imagining the object moving fast. Our data suggest that the lateral mesencephalus participates in different aspects of gait in humans, with the CN and dorsal PPN controlling motor aspects of locomotion and the ventral PPN being involved in integrating sensory information.

How cognitive performance-induced stress can influence right VLPFC activation: an fMRI study in healthy subjects and in patients with social phobia.

The neural bases of interactions between anxiety and cognitive control are not fully understood. We conducted an fMRI study in healthy participants and in patients with an anxiety disorder (social phobia) to determine the impact of stress on the brain network involved in cognitive control. Participants performed two working memory tasks that differed in their level of performance-induced stress. In both groups, the cognitive tasks activated a frontoparietal network, involved in working memory tasks. A supplementary activation was observed in the right ventrolateral prefrontal cortex (VLPFC) in patients during the more stressful cognitive task. Region of interest analyses showed that activation in the right VLPFC decreased in the more stressful condition as compared to the less stressful one in healthy subjects and remain at a similar level in the two cognitive tasks in patients. This pattern was specific to the right when compared to the left VLPFC activation. Anxiety was positively correlated with right VLPFC activation across groups. Finally, left dorsolateral prefrontal cortex (DLPFC) activation was higher in healthy subjects than in patients in the more stressful task. These findings demonstrate that in healthy subjects, stress induces an increased activation in left DLPFC, a critical region for cognitive control, and a decreased activation in the right VLPFC, an area associated with anxiety. In patients, the differential modulation between these dorsal and ventral PFC regions disappears. This absence of modulation may limit anxious patients' ability to adapt to demanding cognitive control tasks.

Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease.

Gait disorders and postural instability, which are commonly observed in elderly patients with Parkinson disease (PD), respond poorly to dopaminergic agents used to treat other parkinsonian symptoms. The brain structures underlying gait disorders and falls in PD and aging remain to be characterized. Using functional MRI in healthy human subjects, we have shown here that activity of the mesencephalic locomotor region (MLR), which is composed of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus, was modulated by the speed of imagined gait, with faster imagined gait activating a discrete cluster within the MLR. Furthermore, the presence of gait disorders in patients with PD and in aged monkeys rendered parkinsonian by MPTP intoxication correlated with loss of PPN cholinergic neurons. Bilateral lesioning of the cholinergic part of the PPN induced gait and postural deficits in nondopaminergic lesioned monkeys. Our data therefore reveal that the cholinergic neurons of the PPN play a central role in controlling gait and posture and represent a possible target for pharmacological treatment of gait disorders in PD.

Endogenous multifractal brain dynamics are modulated by age, cholinergic blockade and cognitive performance.

The intuitive notion that a healthy organism is characterised by regular, homeostatic function has been challenged by observations that a loss of complexity is, in fact, indicative of ill-health. Monofractals succinctly describe complex processes and are controlled by a single time-invariant scaling exponent, H, simply related to the fractal dimension. Previous analyses of resting fMRI time-series demonstrated that ageing and scopolamine administration were both associated with increases in H and that faster response in a prior encoding task was also associated with increased H. We revisit this experiment with a novel, multifractal approach in which fractal dynamics are assumed to be non-stationary and defined by a spectrum of local singularity exponents. Parameterisation of this spectrum was capable of refracting the effects of age, scopolamine and task performance as well as a refining a description of the associated signal changes. Using the same imaging data, we also explored turbulence as a possible mechanism underlying multifractal dynamics. Evidence is provided that Carstaing's model of turbulent information flow from high to low scales has only limited validity, and that scale invariance of energy dissipation is better explained by critical-phase phenomena, supporting the proposition that the brain maintains a state of self-organised criticality.

Brain hyper-reactivity to auditory novel targets in children with high-functioning autism.

Although communication and social difficulties in autism have received a great deal of research attention, the other key diagnostic feature, extreme repetitive behaviour and unusual narrow interests, has been addressed less often. Also known as 'resistance to change' this may be related to atypical processing of infrequent, novel stimuli. This can be tested at sensory and neural levels. Our aims were to (i) examine auditory novelty detection and its neural basis in children with autism spectrum conditions (ASC) and (ii) test for brain activation patterns that correlate quantitatively with number of autistic traits as a test of the dimensional nature of ASC. The present study employed event-related fMRI during a novel auditory detection paradigm. Participants were twelve 10- to 15-year-old children with ASC and a group of 12 age-, IQ- and sex-matched typical controls. The ASC group responded faster to novel target stimuli. Group differences in brain activity mainly involved the right prefrontal-premotor and the left inferior parietal regions, which were more activated in the ASC group than in controls. In both groups, activation of prefrontal regions during target detection was positively correlated with Autism Spectrum Quotient scores measuring the number of autistic traits. These findings suggest that target detection in autism is associated not only with superior behavioural performance (shorter reaction time) but also with activation of a more widespread network of brain regions. This pattern also shows quantitative variation with number of autistic traits, in a continuum that extends to the normal population. This finding may shed light on the neurophysiological process underlying narrow interests and what clinically is called 'need for sameness'.

Reliving lifelong episodic autobiographical memories via the hippocampus: a correlative resting PET study in healthy middle-aged subjects.

We aimed at identifying the cerebral structures whose synaptic function subserves the recollection of lifetime's episodic autobiographical memory (AM) via autonoetic consciousness. Twelve healthy middle-aged subjects (mean age: 59 years +/- 2.5) underwent a specially designed cognitive test to assess the ability to relive richly detailed episodic autobiographical memories from five time periods using the Remember/Know procedure. We computed an index of episodicity (number of Remember responses justified by the recall of specific events and details) and an index of retrieval spontaneity, and additionally an index of semanticized memories (number of Know responses). The regional cerebral blood flow (rCBF) was measured in the resting state, with H(2)O(15) as part of an activation PET study. The indexes were correlated with blood flow using volumes of interest in frontotemporal regions, including hippocampus and voxel-wise analyses in SPM. With both analyses, significant correlations were mainly found between the index of episodicity and rCBF in the medial temporal lobe, including hippocampus, across the five time periods (unlike the index of semanticized memories) and between the spontaneity index and rCBF in the prefrontal areas. These results highlight, in healthy subjects, the distinct role of these two structures in AM retrieval and support the view that the hippocampus is needed for reexperiencing detailed episodic memories no matter how old they are.

Neural correlates of age-related verbal episodic memory decline: a PET study with combined subtraction/correlation analysis.

Using PET, we have determined the neural substrates of age-related verbal episodic memory decline. Twelve young and twelve older healthy volunteers (mean age; 22 and 59 years, respectively) were scanned while performing encoding and retrieval tasks. Retrieval performance was lower in old than in young subjects. The PET data were analyzed using a combined subtraction/correlation approach. Classic subtraction disclosed prefrontal rCBF increases common to both groups, distributed bilaterally during encoding and exclusively right-sided during retrieval, without between-group differences. The correlation analysis between PET activity during encoding and subsequent retrieval performance revealed significant correlations for the left hippocampal region in both groups, but for the right inferior frontal gyrus in the older subjects only. Thus, lower performance in older subjects during an episodic retrieval task may reflect a combination of (i) subtle encoding dysfunction, evidenced by more widespread activity-performance correlations and (ii) less efficient retrieval, as evidenced by unaltered activation pattern (as revealed by the classic subtraction method) despite reduced performance. These exploratory findings suggest the aged brain may be unable to compensate for reduced efficiency of right prefrontal cortex by additional left frontal activation.

Change detection in children with autism: an auditory event-related fMRI study.

Autism involves impairments in communication and social interaction, as well as high levels of repetitive, stereotypic, and ritualistic behaviours, and extreme resistance to change. This latter dimension, whilst required for a diagnosis, has received less research attention. We hypothesise that this extreme resistance to change in autism is rooted in atypical processing of unexpected stimuli. We tested this using auditory event-related fMRI to determine regional brain activity associated with passive detection of infrequently occurring frequency-deviant and complex novel sounds in a no-task condition. Participants were twelve 10- to 15-year-old children with autism and a group of 12 age- and sex-matched healthy controls. During deviance detection, significant activation common to both groups was located in the superior temporal and inferior frontal gyri. During 'novelty detection', both groups showed activity in the superior temporal gyrus, the temporo-parietal junction, the superior and inferior frontal gyri, and the cingulate gyrus. Children with autism showed reduced activation of the left anterior cingulate cortex during both deviance and novelty detection. During novelty detection, children with autism also showed reduced activation in the bilateral temporo-parietal region and in the right inferior and middle frontal areas. This study confirms previous evidence from ERP studies of atypical brain function related to automatic change detection in autism. Abnormalities involved a cortical network known to have a role in attention switching and attentional resource distribution. These results throw light on the neurophysiological processes underlying autistic 'resistance to change'.

The hippocampal region is involved in successful recognition of both remote and recent famous faces.

There is currently a debate regarding the precise role of medial temporal regions in memory, in particular regarding the time scale of their involvement in conscious recollection of information stored in long-term memory. Using event-related fMRI, we have attempted to contribute to this debate by identifying brain regions associated with the successful recognition of famous faces from two different periods: "Old" faces of people who became famous in the 1960s-1970s and "Recent" faces of people who became famous in the 1990s. We demonstrate that the hippocampus is involved in the successful recognition of famous faces from both periods and does not appear to distinguish between these two periods. We also highlight a network of brain regions, including the left prefrontal cortex, the retrosplenial cortex, the temporo-parietal junction, the caudate and the right cerebellum, which is activated in association with successful recognition of famous faces. Finally, an analysis of the results obtained during a post hoc episodic recognition task shows the specific involvement of anterior hippocampus in the successful encoding of the unfamiliar faces, which were presented during the fame decision task, suggesting a functional distinction between anterior and posterior parts of the hippocampus, the former being specifically involved in successful episodic encoding and the latter being associated with successful retrieval of semantic information.