Daniela Smirni

Enhancing memory performance with rTMS in healthy subjects and individuals with Mild Cognitive Impairment: the role of the right dorsolateral prefrontal cortex

A debated question in the literature is the degree of anatomical and functional lateralization of the executive control processes sub-served by the dorsolateral prefrontal cortex (DLPFC) during recognition memory retrieval. We investigated if transient inhibition and excitation of the left and right DLPFC at retrieval by means of repetitive transcranial magnetic stimulation (rTMS) modulate recognition memory performance in 100 healthy controls (HCs) and in eight patients with Mild Cognitive Impairment (MCI). Recognition memory tasks of faces, buildings, and words were used in different experiments. rTMS-inhibition of the right DLPFC enhanced recognition memory in both HCs and MCIs. rTMS-excitation of the same region in HCs deteriorated memory performance. Inhibition of the right DLPFC could modulate the excitability of a network of brain regions, in the ipsilateral as well as in the contralateral hemisphere, enhancing function in HCs or restoring an adaptive equilibrium in MCI.

The role of the prefrontal cortex in familiarity and recollection processes during verbal and non-verbal recognition memory: an rTMS study.

Neuroimaging and lesion studies have documented the involvement of the frontal lobes in recognition memory. However, the precise nature of prefrontal contributions to verbal and non-verbal memory and to familiarity and recollection processes remains unclear. The aim of the current rTMS study was to investigate for the first time the role of the DLPFC in encoding and retrieval of non-verbal and verbal memoranda and its contribution to recollection and familiarity processes. Recollection and familiarity processes were studied using the ROC and unequal variance signal detection methodologies. We found that rTMS delivered over left and right DLPFC at encoding resulted in material specific laterality effects with a disruption of recognition of verbal and non-verbal memoranda. Interestingly, rTMS over DLPFCs at encoding significantly affected both recollection and familiarity. However, at retrieval rTMS did not affect recollection and familiarity. Our results suggest that DLPFC has a degree of functional specialisation and plays an important role in the encoding of verbal and non-verbal memoranda.

Modulating Memory Performance in Healthy Subjects with Transcranial Direct Current Stimulation Over the Right Dorsolateral Prefrontal Cortex.

Objective The role of the Dorsolateral Prefrontal Cortex (DLPFC) in recognition memory has been well documented in lesion, neuroimaging and repetitive Transcranial Magnetic Stimulation (rTMS) studies. The aim of the present study was to investigate the effects of transcranial Direct Current Stimulation (tDCS) over the left and the right DLPFC during the delay interval of a non-verbal recognition memory task. Method 36 right-handed young healthy subjects participated in the study. The experimental task was an Italian version of Recognition Memory Test for unknown faces. Study included two experiments: in a first experiment, each subject underwent one session of sham tDCS and one session of left or right cathodal tDCS; in a second experiment each subject underwent one session of sham tDCS and one session of left or right anodal tDCS. Results Cathodal tDCS over the right DLPFC significantly improved non verbal recognition memory performance, while cathodal tDCS over the left DLPFC had no effect. Anodal tDCS of both the left and right DLPFC did not modify non verbal recognition memory performance. Conclusion Complementing the majority of previous studies, reporting long term memory facilitations following left prefrontal anodal tDCS, the present findings show that cathodal tDCS of the right DLPFC can also improve recognition memory in healthy subjects.

Exploring the Relationship between Semantics and Space

The asymmetric distribution of human spatial attention has been repeatedly documented in both patients and healthy controls. Biases in the distribution of attention and/or in the mental representation of space may also affect some aspects of language processing. We investigated whether biases in attention and/or mental representation of space affect semantic representations. In particular, we investigated whether semantic judgments could be modulated by the location in space where the semantic information was presented and the role of the left and right parietal cortices in this task. Healthy subjects were presented with three pictures arranged horizontally (one middle and two outer pictures) of items belonging to the same semantic category. Subjects were asked to indicate the spatial position in which the semantic distance between the outer and middle pictures was smaller. Subjects systematically overestimated the semantic distance of items presented in the right side of space. We explored the neural correlates underpinning this bias using rTMS over the left and right parietal cortex. rTMS of the left parietal cortex selectively reduced this rightward bias. Our findings suggest the existence of an attentional and/or mental representational bias in semantic judgments, similar to that observed for the processing of space and numbers. Spatial manipulation of semantic material results in the activation of specialised attentional resources located in the left hemisphere.

Cognitive reserve and cognitive performance of patients with focal frontal lesions

ABSTRACT The Cognitive reserve (CR) hypothesis was put forward to account for the variability in cognitive performance of patients with similar degrees of brain pathology. Compensatory neural activity within the frontal lobes has often been associated with CR. For the first time we investigated the independent effects of two CR proxies, education and NART IQ, on measures of executive function, fluid intelligence, speed of information processing, verbal short term memory (vSTM), naming, and perception in a sample of 86 patients with focal, unilateral frontal lesions and 142 healthy controls. We fitted multiple linear regression models for each of the cognitive measures and found that only NART IQ predicted executive and naming performance. Neither education nor NART IQ predicted performance on fluid intelligence, processing speed, vSTM or perceptual abilities. Education and NART IQ did not modify the effect of lesion severity on cognitive impairment. We also found that age significantly predicted performance on executive tests and the majority of our other cognitive measures, except vSTM and GNT. Age was the only predictor for fluid intelligence. This latter finding suggests that age plays a role in executive performance over and above the contribution of CR proxies in patients with focal frontal lesions. Overall, our results suggest that the CR proxies do not appear to modify the relationship between cognitive impairment and frontal lesions. HIGHLIGHTSEffect of cognitive reserve (CR) proxies in focal unilateral lesions.NART IQ accounts for a larger proportion of variance in executive and naming skills.Age predicts performance on executive, fluid intelligence, speed and perception tests.Education and NART IQ did not modify the effect of lesion severity on cognitive impairment.

Combining tDCS with prismatic adaptation for non-invasive neuromodulation of the motor cortex.

Background: Prismatic adaptation (PA) shifts visual field laterally and induces lateralized deviations of spatial attention. Recently, it has been suggested that prismatic goggles are also able to modulate brain excitability, with cognitive after‐effects documented even in tasks not necessarily spatial in nature. Objective: The aim of the present study was to test whether neuromodulatory effects obtained from tDCS and prismatic goggles could interact and induce homeostatic changes in corticospinal excitability. Methods: Thirty‐four subjects were submitted to single‐pulse transcranial magnetic stimulation (TMS) over the right primary motor cortex to measure Input‐Output (IO) curve as a measure of corticospinal excitability. Assessment was made in three experimental conditions: before and after rightward PA and anodal tDCS of the right motor cortex; before and after rightward PA; before and after anodal tDCS of the right motor cortex. Results: A significant decrease of MEPs amplitude and of IO curve slope steepness was found after the combination of rightward PA and anodal tDCS; on the other hand, an increase of MEPs amplitude and of the steepness of IO curve slope on the right motor cortex was found following either rightward PA or anodal tDCS. Conclusion: These findings suggest that priming of motor cortex excitability using PA could be an additional tool to modulate cortical metaplasticity. HIGHLIGHTSPrismatic adaptation and tDCS were used to modulate the right M1.Prismatic adaptation and tDCS were combined to test whether their effects can mutually interact.Single‐pulse TMS were used to measure M1 excitability.Subjects’ M1 excitability significantly increased after either rightward prismatic adaptation or anodal tDCS.Subjects’ IO M1 excitability significantly decreased after the combination of rightward PA and anodal tDCS.

Standardization and validation of a parallel form of the verbal and non verbal recognition memory test in an Italian population sample

In the neuropsychological assessment of several neurological conditions, recognition memory evaluation is requested. Recognition seems to be more appropriate than recall to study verbal and non-verbal memory, because interferences of psychological and emotional disorders are less relevant in the recognition than they are in recall memory paradigms. In many neurological disorders, longitudinal repeated assessments are needed to monitor the effectiveness of rehabilitation programs or pharmacological treatments on the recovery of memory. In order to contain the practice effect in repeated neuropsychological evaluations, it is necessary the use of parallel forms of the tests. Having two parallel forms of the same test, that kept administration procedures and scoring constant, is a great advantage in both clinical practice, for the monitoring of memory disorder, and in experimental practice, to allow the repeated evaluation of memory on healthy and neurological subjects. First aim of the present study was to provide normative values in an Italian sample (n = 160) for a parallel form of a verbal and non-verbal recognition memory battery. Multiple regression analysis revealed significant effects of age and education on recognition memory performance, whereas sex did not reach a significant probability level. Inferential cutoffs have been determined and equivalent scores computed. Secondly, the study aimed to validate the equivalence of the two parallel forms of the Recognition Memory Test. The correlations analyses between the total scores of the two versions of the test and correlation between the three subtasks revealed that the two forms are parallel and the subtasks are equivalent for difficulty.

Relationship between physiological excitatory and inhibitory measures of excitability in the left vs. right human motor cortex and peripheral electrodermal activity

The current study was aimed at investigating the relationships of excitatory and inhibitory circuits of the left vs. right primary motor cortex with peripheral electrodermal activity (EDA). Ten healthy subjects participated in two experimental sessions. In each session, EDA was recorded for 10min from the palmar surface of the left hand. Immediately after EDA recording, Transcranial Magnetic Stimulation (TMS) was used to probe excitatory and inhibitory circuits of the left or right primary motor cortex using two protocols of stimulation: the input-output curve for recording of motor evoked potentials, for testing excitatory circuits; the long-interval cortical inhibition (LICI) protocol, for testing inhibitory circuits. In both cases, motor evoked potentials were recorded with surface electrodes from a contralateral hand muscle. The main results showed that in the right motor cortex, excitatory circuits directly correlate and inhibitory circuits inversely correlate with sympathetic activation. In the left motor cortex, both excitatory and inhibitory circuits are inversely correlated with sympathetic activation. These findings may suggest a bi-hemispheric mode of control of vegetative system by motor cortices, with the right hemisphere mainly involved in sympathetic control.

Modulating phonemic fluency performance in healthy subjects with transcranial magnetic stimulation over the left or right lateral frontal cortex

&NA; A growing body of evidence have suggested that non‐invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can improve the performance of aphasic patients in language tasks. For example, application of inhibitory rTMS or tDCs over the right frontal lobe of dysphasic patients resulted in improved naming abilities. Several studies have also reported that in healthy controls (HC) tDCS application over the left prefrontal cortex (PFC) improve performance in naming and semantic fluency tasks. The aim of this study was to investigate in HC, for the first time, the effects of inhibitory repetitive TMS (rTMS) over left and right lateral frontal cortex (BA 47) on two phonemic fluency tasks (FAS or FPL). 44 right‐handed HCs were administered rTMS or sham over the left or right lateral frontal cortex in two separate testing sessions, with a 24 h interval, followed by the two phonemic fluency tasks. To account for possible practice effects, an additional 22 HCs were tested on only the phonemic fluency task across two sessions with no stimulation. We found that rTMS‐inhibition over the left lateral frontal cortex significantly worsened phonemic fluency performance when compared to sham. In contrast, rTMS‐inhibition over the right lateral frontal cortex significantly improved phonemic fluency performance when compared to sham. These results were not accounted for practice effects. We speculated that rTMS over the right lateral frontal cortex may induce plastic neural changes to the left lateral frontal cortex by suppressing interhemispheric inhibitory interactions. This resulted in an increased excitability (disinhibition) of the contralateral unstimulated left lateral frontal cortex, consequently enhancing phonemic fluency performance. Conversely, application of rTMS over the left lateral frontal cortex may induce a temporary, virtual lesion, with effects similar to those reported in left frontal patients. HighlightsThis study investigated effect of inhibitory rTMS over left or right lateral frontal cortex in healthy subjects during a phonemic fluency task.rTMS‐inhibition over the right lateral frontal cortex significantly improved phonemic fluency performance.rTMS‐inhibition over the left lateral frontal cortex significantly worsened phonemic fluency performance.This study offer hints to the possible use of brain stimulation to improve performance on phonemic fluency tasks in patients with frontal lesions.

Early detection of memory impairments in older adults: standardization of a short version of the verbal and nonverbal Recognition Memory Test

In several neurological conditions, in elderly and cognitively impaired subjects, memory functioning must be evaluated to early detect the cognitive deterioration processes. In particular, recognition memory assessment is an essential step in the clinical and neuropsychological evaluation of early memory impairments. The Recognition Memory Test (RMT) developed by Smirni et al. (G Ital Psicol XXXVII(1):325–343, 2010) is an effective instrument to assess verbal and nonverbal recognition memory in the Italian population. The current study provides a new, brief, and reliable RMT format to evaluate recognition memory on elderly subjects and it reports normative data in an older adult Italian population sample (including 100 participants well distributed across sex, education, and age categories). The shortened version of RMT keeps the administration procedures and materials of the original Italian RMT constant, i.e., words, faces, and buildings. Multiple regression analysis revealed significant effects of age and educational level on performance but no effect of sex. Inferential cutoffs have been determined and equivalent scores computed. The availability of equivalent scores for the Recognition Memory Test will prove useful in the clinical evaluation of patients’ memory profiles.