Giuseppa Renata Mangano

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.

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.

The role of posterior parietal cortex in spatial representation of time: A TMS study

The existence of a spatial representation of time, where temporal intervals are represented on a mental temporal line (MTL), oriented in ascending order from left to right, was demonstrated manipulating spatial attention by means of Prismatic Adaptation (PA). In young healthy subjects, prisms adaptation inducing a rightward shift of spatial-attention produced an overestimation of time intervals, whereas prisms adaptation inducing a leftward shift of spatial-attention produced an underestimation of time intervals [4]. The aim of the present study was to investigate the neural basis mediating the effects of PA on spatial time representation. Posterior-Parietal-Cortex (PPC) is the best candidate to discharge this function. Indeed, neuropsychological and neurophysiological studies designate right-PPC as the site of space-time interaction [1,3,7]. Concerning the neural bases of PA procedures, left and right-PPC are involved in different phases of PA procedure [2,5, 6]. Here we investigated, by using TMS, the role of the Posterior-Parietal-Cortex (PPC) in spatial representation of time and in cerebral plasticity phenomena mediating prismatic adaptation effects on time processing. To this aim, healthy subjects were submitted to a tem-

Benign myoclonic epilepsy in infancy followed by childhood absence epilepsy

Benign myoclonic epilepsy in infancy (BMEI) is a rare syndrome included among idiopathic generalized epilepsies (IGE) and syndromes with age-related onset. Recently, it has been shown that a few patients with BMEI later had other epilepsy types mainly IGE but never childhood absence epilepsy (CAE). We report a patient who at 11 months of age showed isolated myoclonic jerks occurring several times a day. The ictal video-EEG and polygraphic recording revealed generalized discharge of spike-wave (SW) lasting 1-2s associated with isolated bilateral synchronous jerk involving mainly the upper limbs controlled by valproic acid (VPA). At 6 years and 8 months the child developed a new electroclinical feature recognized as CAE. The ictal EEG disclosed a burst of rhythmic 3 Hz generalized SW. Our case is the first patient with BMEI reported in the literature who later developed a CAE. This finding suggests a common neurobiological and genetic link between different age-related epileptic phenotypes.

The role of posterior parietal cortices on prismatic adaptation effects on the representation of time intervals

Previous studies provided evidence of an ascending left-to-right spatial representation of time durations by using a technique affecting high levels of spatial cognition, i.e. prismatic adaptation (PA). Indeed, PA that induced a leftward aftereffect distorted time representation toward an underestimation, while PA that induced a rightward aftereffect distorted time representation toward an overestimation. The present study advances previous findings on the effects of PA on time by investigating the neural basis subtending these effects. We focused on the posterior parietal cortex (PPC) since it is involved in the PA procedure and also in the formulation of the spatial representation of time. We conducted two experiments where right-handed healthy adults were submitted to a time task, before and after PA, that could induce a leftward or rightward aftereffect. Repetitive TMS (rTMS) was used to inhibit the left or right PPC before PA administration. In a first experiment the time task consisted of reproducing an half duration (time bisection task) by pressing a key and the participants responded and adapted to prisms with their right hand. In a second experiment the time task consisted of reproducing a whole duration (time reproduction task) by pressing a key and the participants responded and adapted to prisms with their left hand. We found an abolition of the effects of PA on time when rTMS was delivered on the left and not on the right PPC, regardless of the task and moreover, when the participants responded and adapted with the right hand and also with the left hand. This result suggests a direct involvement of the left PPC in the interactive process, between spatial modulations induced by PA and the spatial representation of time, that does not depend on motor processes. This study provides useful results for future investigations on the neural mechanisms subtending the effects of PA on spatial representations.

Processing past tense in the left cerebellum

We report the case of a patient with ischemic lesion of the left cerebellum, who showed specific deficits in processing past versus future tense of action verbs. These findings confirm, in the presence of cerebellar damage, previous results obtained with transcranial magnetic stimulation in healthy subjects and suggest a specificity of the left cerebellum for preparation of responses to the past tense of action verbs. As part of the procedural brain, the cerebellum could play a role in applying the linguistic rules for selection of morphemes typical of past and future tense formation.

West syndrome followed by juvenile myoclonic epilepsy: a coincidental occurrence?

BackgroundWest syndrome is an age-dependent epilepsy with onset peak in the first year of life whose aetiology may be symptomatic or cryptogenic. Long-term cognitive and neurological prognosis is usually poor and seizure outcome is also variable. Over the past two decades a few patients with favourable cognitive outcome and with total recovery from seizures were identified among the cryptogenic group suggesting an idiopathic aetiology. Recent research has described two children with idiopathic WS who later developed a childhood absence epilepsy.Case presentationWe reviewed the medical records of patients with West syndrome admitted to the our Child Neuropsychiatry Unit in the last 15 years in order to know the clinical evolution of infantile spasms.We report a child with West syndrome with onset at 8 months of age followed by some clusters of bilateral, arrhythmic myoclonic jerks of the upper limbs, mainly on awakening, synchronous with the generalized discharges of 4 Hz spike-wave occurring at 12 years of age and by co-occurrence of a later generalized tonic-clonic seizure at 14 years and four months, both sensitive to Levetiracetam suggesting a juvenile myoclonic epilepsy.ConclusionsThis unusual evolution, never previously reported, suggests that both electroclinical features mentioned above may share some pathophysiological processes genetically determined which produce a susceptibility to seizure and emphasizes that the transition between different age-related epileptic phenotypes may involve also the West syndrome.

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.

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.